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Perini JA, Dias AS, Gusmão L, Skaf LB, Elias ABR, Basta PC, Carvalho MA, Suarez-Kurtz G. UGT1A1 polymorphisms and metabolic phenotypes in indigenous peoples from the Brazilian Amazon. Pharmacogenet Genomics 2025; 35:153-158. [PMID: 40277150 DOI: 10.1097/fpc.0000000000000566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
OBJECTIVES To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon. METHODS Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes. RESULTS All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes. CONCLUSION This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant ( UGT1A1 * 80 ) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.
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Affiliation(s)
- Jamila A Perini
- Laboratório de Pesquisa de Ciências Farmacêuticas (LAPESF), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | | | - Leonor Gusmão
- Laboratório de Diagnóstico por DNA, UERJ, Rio de Janeiro, Brazil
| | - Larissa B Skaf
- Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil
| | - Anna Beatriz R Elias
- Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil
| | - Paulo C Basta
- Departamento de Endemias Samuel Pessoa, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz (ENSP/Fiocruz), Rio de Janeiro, Brazil
| | - Marcelo A Carvalho
- Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil
- Instituto Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Guilherme Suarez-Kurtz
- Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil
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Tovar-Parra D, Gutiérrez-Castañeda LD. Polygenic Risk Score Analysis of 37 SNPs Associated with Melanoma Risk in Colombian Population. Int J Mol Sci 2025; 26:4674. [PMID: 40429816 PMCID: PMC12112468 DOI: 10.3390/ijms26104674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/13/2025] [Accepted: 04/23/2025] [Indexed: 05/29/2025] Open
Abstract
Melanoma incidence is increasing, with distinct genetic and clinical patterns observed in the Latin American population. This study aimed to evaluate melanoma risk in a Colombian cohort through polygenic risk analysis using 37 variants across nine genes previously associated with melanoma. We performed polygenic risk score (PRS) analysis on 85 melanoma patients and 165 controls. Genotyping was performed for 37 melanoma-associated SNPs, and on the basis of previous GWAS reports, individual PRSs were calculated for each participant. The participants were then stratified into quartiles to examine risk gradients. In addition, phenotypic features such as eye and hair color were evaluated, and genetic models and haplotype analyses were performed, adjusting for sex and family history of cancer. PRS quartile stratification revealed a clear risk gradient. Notably, 31.8% of the melanoma cases were clustered in the highest-risk quartile (Q4), with a maximum PRS of 1.04. Variants in TYR, TYRP1, CDKN2A, and HERC2 significantly contributed to risk, and light brown eye and hair colors were strongly associated with increased melanoma risk. Moreover, a protective haplotype in the OCA2-HERC2 region was identified among males. The integration of the PRS with clinical and phenotypic factors has potential for improving melanoma risk stratification in the Colombian population, warranting further investigation in larger, diverse cohorts.
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Affiliation(s)
- David Tovar-Parra
- General Dermatology Group, Hospital Universitario Centro Dermatologico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia;
- Institut National de la Recherche Scientifique INRS, Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada
| | - Luz Dary Gutiérrez-Castañeda
- General Dermatology Group, Hospital Universitario Centro Dermatologico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia;
- Research Institute, Basic Health Sciences Group, Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá 111221, Colombia
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Moncada Madero J, Mogollón Olivares F, Suárez Medellín D, Coronel Guzmán A, Casas-Vargas A, Usaquén Martínez W. The Analysis of Autosomal STRs Draws the Current Genetic Map and Evolutionary History of Northernmost South America. Genes (Basel) 2025; 16:574. [PMID: 40428396 PMCID: PMC12110986 DOI: 10.3390/genes16050574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 05/29/2025] Open
Abstract
OBJECTIVES To analyze Colombia's current human population, we employed a population genetics approach enriched by genealogical, demographic, cultural, and historical data to learn about its evolutionary history and to elucidate ethnic belonging and relationship patterns between its various population groups. MATERIALS AND METHODS This study relied on ten autosomal microsatellite markers (STRs) from 1364 individuals surveyed throughout the country. Aside from employing descriptive population genetics, substructure, and distance analysis, this investigation evaluated genealogical, demographic, cultural, and historical data gathered from fieldwork surveys. RESULTS We present a genetic diversity and ethnic belonging map of Colombia that suggests a nine-population classification (under Afro-descendant, Native American, and Admixed ethnicity labels) that reveals traces of evolutionary processes discussed in the light of the recent literature based on modern molecular markers. Colombia's genetic trace from Africa varies among territories, as shown here by two differentiated Afro ancestral components, Chocó and San Andrés, in addition to the Afro admixture category. Some Native American peoples like the Wayúu, Zenú, Ticuna, Huitoto, and Cocama have a genetic configuration that remains relatively preserved. Nevertheless, other self-determined indigenous peoples who remain in their ancestral territories exhibit genetic introgression that is also reflected by their acculturation levels such as the Pijaos, Kankuamos, and Mokaná. The population classified as European admixture also shows an ancestral component that seems to be more fixed throughout neighboring territories but whose fluctuation depends on its specific demographic histories. CONCLUSIONS This study combines STRs, a targeted sampling strategy, and advanced analytical tools to explore Colombia's genetic diversity and evolutionary history. Locally, these findings enhance the understanding of genetics in a post-conflict society, crucial for human identification. Globally, they contribute to human population genetics, helping address evolutionary questions using data from diverse human ancestries and geographies.
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Affiliation(s)
| | | | | | | | | | - William Usaquén Martínez
- Grupo de Genética de Poblaciones e Identificación, Instituto de Genética—Universidad Nacional de Colombia, Sede Bogotá 111321, Colombia; (J.M.M.); (F.M.O.); (D.S.M.); (A.C.G.); (A.C.-V.)
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Unigarro-Martinez MF, Munevar-Velandia A, Aristizabal-Duque R, Rodriguez-Martinez CE. The Applicability of Existing Reference Equations for the 6-Minute Walk Test in Healthy Children and Adolescents Living in a City at a High Altitude. Pediatr Pulmonol 2025; 60:e71145. [PMID: 40432303 DOI: 10.1002/ppul.71145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 04/12/2025] [Accepted: 05/18/2025] [Indexed: 05/29/2025]
Abstract
OBJECTIVES This study aimed to evaluate the applicability of existing 6MWT reference equations to healthy children and adolescents living in a high-altitude city. METHODS Healthy children aged 5 to 15 years attending two non-randomly selected schools in Bogotá were invited to participate in the study. All participants performed the 6MWT according to the European Respiratory Society/American Thoracic Society technical standards. To identify the model or set of 6MWT equations that best predicted individually measured 6MWT values in our population, we identified the narrowest limits of agreement (LOA) (mean difference between measured and predicted values ± 1.96 SD) after constructing Bland-Altman plots. We performed separate analyzes based on sex and onset of puberty, which was assumed to occur at 12 years of age for girls and 13 years of age for boys. RESULTS 105 children and adolescents (61 girls, 58.1%) with a mean age of 10.04 years (±2.21), ranging from 6 to 15 years, were evaluated. We determined that equations derived from two different studies conducted in Brazil, de Assis, and Oliveira 6MWT equations provided the narrowest LOA in the Bland-Altman plots for the individually-measured 6MWT values for all study participants, except for the older female participants who obtained narrower LOA with the Ulrich equations. CONCLUSION For the mean walked distance of the 6MWT, we have provided information on the 6MWT predictive equations that may be most appropriate for use in healthy children living in Bogota, Colombia, a city at 2640 m altitude.
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Affiliation(s)
| | | | | | - Carlos E Rodriguez-Martinez
- Department of Pediatric Pulmonology, School of Medicine, Universidad El Bosque, Bogota, Colombia
- Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia
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Castillo A, Gomes V, Ossa H, Ribeiro B, Prata MJ, Rondón F, Simão F, Gusmão L. An overview of the mtDNA diversity across the Colombian Andean region. Forensic Sci Int Genet 2025; 78:103288. [PMID: 40286600 DOI: 10.1016/j.fsigen.2025.103288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/15/2025] [Accepted: 04/23/2025] [Indexed: 04/29/2025]
Abstract
In Colombia, a country in the northwest corner of South America, populations are highly diverse due to the intercontinental admixture of Native Americans, European settlers, and enslaved Africans. While genetic diversity has been largely assessed based on autosomal markers, studies on mtDNA are much scarcer, allowing only a fragmentary view of the distribution of maternal lineages in the country. In this study the genetic diversity of maternal lineages in Colombian Andean populations was interrogated to infer whether the pattern of structuring was in line with the different colonization histories of the departments within the region. The ultimate goal was to establish a haplotype database for forensic purposes. In a total of 458 individuals born and residing in the departments of the Andean region, haplotypes of the total mtDNA control region were determined and assigned to the corresponding haplogroups. Across the 10 departments, haplotype diversities ranged between 0.9665 and 0.9967, and power of exclusion between 0.9208 and 0.9845. A component ascribed to be of Native American ancestry prevailed in all departments, where 89.27 % of haplotypes in the total sample belonged to mtDNA macro-haplogroups A2, B4, C1, and D. The remaining lineages were of Eurasian (6.65 %) or African (4.08 %) origin. Pairwise FST values showed signs of genetic differentiation, but still only reached statistical significance when Risaralda or Cundinamarca were compared with other populations. Principal component analysis showed that the population structure was mainly due to some differences in Native American substrates. The results obtained highlighted a heterogeneity within Andean populations that must be considered when developing mtDNA haplotype databases for forensic purposes. In this context, the use of specific databases is recommended for the departments of Risaralda and Cundinamarca, while the other departments can rely on a single haplotype frequency database.
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Affiliation(s)
- Adriana Castillo
- Laboratorio de Genética, Escuela de Medicina, Universidad Industrial de Santander (UIS), Bucaramanga, Colombia.
| | - Verónica Gomes
- Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - Humberto Ossa
- Laboratorio de Genética y Biología Molecular, Bogotá, Colombia; Facultad de Ciencias Biológicas, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Bibiana Ribeiro
- Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Maria João Prata
- Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal
| | - Fernando Rondón
- Laboratorio de Genética y Biotecnología, Escuela de Biología, Universidad Industrial de Santander (UIS), Bucaramanga, Colombia
| | - Filipa Simão
- Chemistry Department, Forensic Science Program, Towson University, Towson, MD, USA
| | - Leonor Gusmão
- DNA Diagnostic Laboratory (LDD), State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
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Zambrano-O YT, Mejía-Garcia A, Morales PD, Tsao HM, Rey-Vargas L, Montero-Ovalle W, Huertas-Caro CA, Sanabria-Salas MC, Riaño-Moreno J, Rodriguez JL, Orozco CA, Lopez-Kleine L, Jordan IK, Serrano-G SJ. Inference of genetic ancestry from a multi-gene cancer panel in Colombian women with cancer. Breast Cancer Res Treat 2025; 210:251-259. [PMID: 39643752 PMCID: PMC11930861 DOI: 10.1007/s10549-024-07557-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 11/06/2024] [Indexed: 12/09/2024]
Abstract
INTRODUCTION Cancer health disparities among racial and ethnic populations significantly burden health systems due to unequal access to early detection, treatment, and healthcare resources. These disparities lead to worse outcomes and increased costs from delayed diagnoses, advanced treatments, and prolonged care. Genetic differences can also influence cancer susceptibility and treatment response, thus analyzing genetic ancestry is essential for uncovering genetic factors that may contribute to these disparities. Utilizing data from clinical multigene cancer panels to infer genetic ancestry offers a valuable approach to understand population structure and the impact of individual ancestries in development of complex diseases. AIM To evaluate the accuracy of global ancestry inference using genetic markers from the TruSight™ Hereditary Cancer Panel, which was used to investigate hereditary cancer syndromes in a cohort of 116 female cancer patients at the Colombian National Cancer Institute. Additionally, to compare these results with genetic ancestry estimations from traditional genome-wide markers. RESULTS Our results demonstrate a strong correlation between global genetic ancestry inferred with markers captured from TruSightTM panel (4785 markers) and Whole Genome Sequencing (WGS, 8 million markers in admixed populations. The correlation values were 0.96 (p < 0.0001) for the Native American and European ancestry components, and 0.99 (p < 0.0001) for the African ancestry fraction. Genetic ancestry mean proportions in the Colombian cohort were 45.7%, 46.2%, and 8.11% for the European, the Native American, and the African components, respectively. CONCLUSION This study demonstrates the accuracy of ancestry inference from clinical panel data offering a promising approach for understanding cancer health disparities in admixed populations.
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Affiliation(s)
- Yina T Zambrano-O
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia.
- Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia.
| | | | - P Daniela Morales
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia
| | - Hsuan Megan Tsao
- Department of Human Genetics, McGill University, Montreal, Canada
| | - Laura Rey-Vargas
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
| | - Wendy Montero-Ovalle
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia
| | - Carlos A Huertas-Caro
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
| | - M C Sanabria-Salas
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, M5G 2C1, Canada
| | - Julián Riaño-Moreno
- Departamento de Patología y Oncología Molecular, Instituto Nacional de Cancerología, Bogotá, Colombia
- Faculty of Medicine, Universidad Cooperativa de Colombia, Villavicencio, Colombia
| | - Juliana L Rodriguez
- Grupo de Investigación Clínica y Epidemiológica, Instituto Nacional de Cancerología, Bogotá, Colombia
- Departamento de Ginecología y Obstetricia, Universidad Nacional de Colombia - sede Bogotá, Bogotá, Colombia
| | - Carlos A Orozco
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia
- Grupo de Apoyo y Seguimiento Para La Investigación, Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Liliana Lopez-Kleine
- Grupo de Investigación en Bioinformática y Biología de Sistemas, Departamento de Estadística, Universidad Nacional de Colombia, Bogotá, Colombia
| | - I King Jordan
- Bioinformatics Department, Georgia Institute of Technology, Atlanta, USA
| | - Silvia J Serrano-G
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Cl. 1 #9-85, Bogotá, Colombia.
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Sanabria-Salas MC, Rivera-Herrera AL, Manotas MC, Guevara G, Gómez AM, Medina V, Tapiero S, Huertas A, Nuñez M, Torres MZ, Riaño-Moreno J, Parra-Medina R, Mejía JC, Carvajal-Carmona LG. Building a hereditary cancer program in Colombia: analysis of germline pathogenic and likely pathogenic variants spectrum in a high-risk cohort. Eur J Hum Genet 2025:10.1038/s41431-025-01807-y. [PMID: 40065011 DOI: 10.1038/s41431-025-01807-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 01/11/2025] [Accepted: 02/03/2025] [Indexed: 04/30/2025] Open
Abstract
Genetic studies in Latin America have expanded, but further efforts are needed to understand cancer susceptibility genes beyond BRCA1 and BRCA2, especially by characterizing the prevalence and spectrum of pathogenic or likely pathogenic variants (PVs) in the region. This study aimed to determine the frequency of hereditary cancer syndromes (HCS) in Colombians with solid tumors and to characterize the spectrum of PVs. Using data from the Colombia's largest Institutional Hereditary Cancer Program, we included patients aged ≥18 years with solid tumors who met HCS criteria and were offered genetic testing with a 105-cancer gene panel. We calculated the prevalence of PVs and HCS by cancer type (beyond breast) and gene. For patients with breast cancer, we examined genotype-phenotype correlations with molecular subtypes and stratified positivity rates by different genetic testing criteria. Among 769 patients, we identified 216 PVs in 43 genes in 197 patients (26%). Thirty-three PVs were recurrent. Autosomal HCS was found in 21% (160/769) of patients (159 dominant, one recessive), while 5% (37/769) were heterozygous carriers of PVs in autosomal recessive genes. In 42% (321/769) of the cases, only one or more variants of uncertain significance (VUS) were identified, whereas 33% (251/769) had neither PVs nor VUS detected (negative results). HCS prevalence varied by cancer type (11-26%). The triple-negative subtype and bilateral presentation were strong predictors of inherited breast cancer. Our study reveals a significant presence of PVs among high-risk Colombian patients with solid tumors, underscoring the importance of genetic counseling and testing in the region.
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Affiliation(s)
- María Carolina Sanabria-Salas
- Subdirección de Investigaciones, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia.
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia.
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
| | | | | | - Gonzalo Guevara
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Ana Milena Gómez
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Vilma Medina
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Sandra Tapiero
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Antonio Huertas
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Marcela Nuñez
- Subdirección de Investigaciones, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Miguel Zamir Torres
- Subdirección de Investigaciones, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Julián Riaño-Moreno
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
- Medical School, Universidad Cooperativa de Colombia, Villavicencio, Colombia
| | - Rafael Parra-Medina
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
- Research Institute, Fundación Universitaria de Ciencias de la Salud, Bogotá, D.C, Colombia
| | - Juan Carlos Mejía
- Subdirección Médica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
| | - Luis G Carvajal-Carmona
- Office of Academic Diversity, Division of Diversity, Equity and Inclusion, University of California at Davis, Davis, CA, USA.
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Davis, CA, USA.
- Genome Center, University of California Davis, Davis, CA, USA.
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Gusmão L, Antão-Sousa S, Faustino M, Abovich MA, Aguirre D, Alghafri R, Alves C, Amorim A, Arévalo C, Baldassarri L, Barletta-Carrillo C, Berardi G, Bobillo C, Borjas L, Braganholi DF, Brehm A, Builes JJ, Cainé L, Carvalho EF, Carvalho M, Catelli L, Cicarelli RMB, Contreras A, Corach D, Di Marco FG, Diederiche MV, Domingues P, Espinoza M, Fernandéz JM, García MG, García O, Gaviria A, Gomes I, Grattapaglia D, Henao J, Hernandez A, Ibarra AA, Lima G, Manterola IM, Marrero C, Martins JA, Mendoza L, Mosquera A, Nascimento EC, Onofri V, Pancorbo MM, Pestano JJ, Plaza G, Porto MJ, Posada YC, Rebelo ML, Riego E, Rodenbusch R, Rodríguez A, Rodríguez A, Sanchez-Diz P, Santos S, Simão F, Siza Fuentes LM, Sumita D, Tomas C, Toscanini U, Trindade-Filho A, Turchi C, Vullo C, Yurrebaso I, Pereira V, Pinto N. X-chromosomal STRs: Metapopulations and mutation rates. Forensic Sci Int Genet 2025; 76:103232. [PMID: 39893847 DOI: 10.1016/j.fsigen.2025.103232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 01/15/2025] [Accepted: 01/26/2025] [Indexed: 02/04/2025]
Abstract
The analysis of STRs located on the X chromosome has been one of the strategies used to address complex kinship cases. Its usefulness is, however, limited by the low availability of population haplotype frequency data and lack of knowledge on the probability of mutations. Due to the large amount of data required to obtain reliable estimates, it is important to investigate the possibility of grouping data from populations with similar profiles when calculating these parameters. To better understand the partition of genetic diversity among human populations for the X-STRs most used in forensics, an analysis was carried out based on data available in the literature and new data (23,949 haplotypes in total; from these 10,445 new) obtained through collaborative exercises within the Spanish and Portuguese Working Group of the International Society for Forensic Genetics. Based on the available population data, a similarity in X-STR profiles was found in European populations, and in East Asian populations, except for some isolates. A greater complexity was found for African, South American, and South and Southeast Asian populations, preventing their grouping into large metapopulations. New segregation data on 2273 father/mother/daughter trios were also obtained, aiming for a more thorough analysis of X-STR mutation rates. After combining our data with published information on father/mother/daughter trios, no mutations were detected in 13 out of 37 loci analyzed. For the remaining loci, mutation rates varied between 2.68 × 10-4 (DXS7133) and 1.07x10-2 (DXS10135), being 5.2 times higher in the male (4.16 ×10-3) than in the female (8.01 ×10-4) germline.
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Affiliation(s)
- L Gusmão
- DNA Diagnostic Laboratory, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - S Antão-Sousa
- Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Departamento de Biologia, Faculdade de Ciências da Universidade do Porto (FCUP), Porto, Portugal
| | - M Faustino
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Departamento de Biologia, Faculdade de Ciências da Universidade do Porto (FCUP), Porto, Portugal
| | - M A Abovich
- Banco Nacional de Datos Genéticos, Buenos Aires, Argentina and Sección Histocompatibilidad, Unidad Inmunología e Histocompatibilidad, Hospital General de Agudos Dr. Carlos G. Durand, CABA, Buenos Aires, Argentina
| | - D Aguirre
- Laboratorio Genes SAS, Medellín, Colombia
| | - R Alghafri
- General Department of Forensic Sciences and Criminology, Dubai Police General Head Quarters, Dubai, United Arab Emirates
| | - C Alves
- Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal
| | - A Amorim
- Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Departamento de Biologia, Faculdade de Ciências da Universidade do Porto (FCUP), Porto, Portugal
| | - C Arévalo
- Laboratorio Biología-ADN, Comisaría General de Policía Científica, Madrid, Spain and Instituto Universitario de Investigación en Ciencias Policiales (IUICP), Universidad de Alcalá de Henares, Madrid, Spain
| | - L Baldassarri
- Laboratorio di Genetica Forense de la Università Cattolica del Sacro Cuore di Roma, Rome, Italy
| | - C Barletta-Carrillo
- Laboratorio de Genética Humana, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - G Berardi
- PRICAI - Fundación Favaloro, Buenos Aires, Argentina
| | - C Bobillo
- Servicio de Huellas Digitales Genéticos (SHDG) and Cátedra de Genética y Bioquímica Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina
| | - L Borjas
- Laboratorio de Genética Molecular, Unidad de Genética Médica, Facultad de Medicina, Universidad del Zulia, Zulia, Venezuela
| | - D F Braganholi
- Laboratório de Investigação de Paternidade-NAC, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil
| | - A Brehm
- Laboratório de Genética Humana, Universidade da Madeira, Campus da Penteada, Funchal, Portugal
| | - J J Builes
- Laboratorio Genes SAS, Medellín, Colombia
| | - L Cainé
- Serviço de Genética e Biologia Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Norte, Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Portugal
| | - E F Carvalho
- DNA Diagnostic Laboratory, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - M Carvalho
- Serviço de Genética e Biologia Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Centro, Coimbra, Portugal
| | - L Catelli
- DNA Forensic Laboratory, Argentinean Forensic Anthropology Team (EAAF), Córdoba, Argentina
| | - R M B Cicarelli
- Laboratório de Investigação de Paternidade-NAC, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil
| | - A Contreras
- Laboratorio Regional de Genética Forense - Poder Judicial de Rio Negro, Rio Negro, Argentina
| | - D Corach
- Servicio de Huellas Digitales Genéticos (SHDG) and Cátedra de Genética y Bioquímica Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina
| | - F G Di Marco
- Laboratorio ManLab, Area de Filiaciones, Buenos Aires, Argentina
| | - M V Diederiche
- Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz - UESC, Ilhéus, Bahia, Brazil
| | - P Domingues
- DNA Diagnostic Laboratory, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - M Espinoza
- Departamento de Ciencias Forenses, Sección de Bioquímica, Unidad de Genética Forense, Poder Judicial, San José, Costa Rica
| | - J M Fernandéz
- Departamento de Biología, Servicio de Criminalística, Dirección General de la Policía y la Guardia Civil, ámbito Guardia Civil, Spain
| | - M G García
- Laboratorio ManLab, Area de Filiaciones, Buenos Aires, Argentina
| | - O García
- Sección de Genética Forense, Area de Laboratorio Ertzaintza, Bizkaia, Spain
| | - A Gaviria
- Laboratorio de Genética Molecular and Hemocentro Nacional - Cruz Roja Ecuatoriana, Quito, Ecuador
| | - I Gomes
- Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - D Grattapaglia
- Heréditas Tecnologia em Análise de DNA, Brasília, Brazil
| | - J Henao
- Laboratorio de Genética Médica, Universidad Tecnológica de Pereira, Facultad de Ciencias de la Salud, Pereira, Colombia
| | - A Hernandez
- Instituto Nacional de Toxicología y Ciencias Forenses, Delegación de Canarias, Santa Cruz de Tenerife, Spain
| | - A A Ibarra
- Laboratorio IdentiGEN - Universidad de Antioquia, Medellín, Colombia
| | - G Lima
- Serviço de Genética e Biologia Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Norte, Porto, Portugal
| | - I M Manterola
- Servicio Genómica - SGIker - Universidad del País Vasco (UPV-EHU), Bilbao, Spain
| | - C Marrero
- Laboratorio Genomik C.A., Valencia, Venezuela
| | - J A Martins
- Research Centre for Biochemistry and Molecular Biology at the Medical School of São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil
| | - L Mendoza
- Laboratorio Genes SAS, Medellín, Colombia
| | - A Mosquera
- Forensic Genetics Unit, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - E C Nascimento
- Coordenação de Genética Forense, Departamento de Polícia Técnica da Bahia, Salvador, Brazil
| | - V Onofri
- Legal Medicine Unit, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy
| | - M M Pancorbo
- Banco de ADN, Universidad del País Vasco (UPV/EHU), Vitoria, Gasteiz, Spain
| | - J J Pestano
- Laboratorio de Genética Forense, Facultad de Medicina, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain
| | - G Plaza
- NEODIAGNOSTICA, SL, Lleida, Spain
| | - M J Porto
- Serviço de Genética e Biologia Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Centro, Coimbra, Portugal
| | - Y C Posada
- Laboratorio IdentiGEN - Universidad de Antioquia, Medellín, Colombia
| | - M L Rebelo
- Serviço de Genética e Biologia Forenses, Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Norte, Porto, Portugal
| | - E Riego
- Unidad de Parentesco e Identificación Humana por ADN, Referencia Laboratorio Clínico, Dominican Republic
| | - R Rodenbusch
- Laboratório PeritosLab Forense, Porto Alegre, Brazil
| | - A Rodríguez
- Departamento de Ciencias Forenses, Sección de Bioquímica, Unidad de Genética Forense, Poder Judicial, San José, Costa Rica
| | - A Rodríguez
- Forensic Genetics Unit, University of Santiago de Compostela, Santiago de Compostela, Spain
| | | | - S Santos
- Human and Medical Genetics Laboratory, Federal University of Pará, Belém, Brazil
| | - F Simão
- DNA Diagnostic Laboratory, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | | | - D Sumita
- Genomic Engenharia Molecular Ltda., São Paulo, Brasil
| | - C Tomas
- Section of Forensic Genetics - Department of Forensic Medicine, Faculty of Health and Medical Sciences - University of Copenhagen, Copenhagen, Denmark
| | - U Toscanini
- PRICAI - Fundación Favaloro, Buenos Aires, Argentina
| | - A Trindade-Filho
- Instituto de Pesquisa de DNA Forense - Polícia Civil do Distrito Federal, Brasília, Brazil
| | - C Turchi
- Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy
| | - C Vullo
- DNA Forensic Laboratory, Argentinean Forensic Anthropology Team (EAAF), Córdoba, Argentina
| | - I Yurrebaso
- Sección de Genética Forense, Area de Laboratorio Ertzaintza, Bizkaia, Spain
| | - V Pereira
- Section of Forensic Genetics - Department of Forensic Medicine, Faculty of Health and Medical Sciences - University of Copenhagen, Copenhagen, Denmark
| | - N Pinto
- Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal; Centro de Matemática da Universidade do Porto (CMUP), Porto, Portugal.
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Arnaiz-Villena A, Lledo T, Silvera-Redondo C, Juarez I, Vaquero-Yuste C, Martin-Villa JM, Suarez-Trujillo F. The Origin of Amerindians: A Case Study of Secluded Colombian Chimila, Wiwa, and Wayúu Ethnic Groups and Their Trans-Pacific Gene Flow. Genes (Basel) 2025; 16:286. [PMID: 40149438 PMCID: PMC11942480 DOI: 10.3390/genes16030286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/24/2025] [Accepted: 02/08/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND/OBJECTIVES The Human Leukocyte Antigen (HLA) system is composed of a set of genes that codify glycoproteins presenting antigenic proteins to clonotypic T cell receptors in order to start the immune response. Class I and Class II classical loci exhibit high allelic diversity; some of them (or their specific combinations that form haplotypes) are quasi-specific or highly frequent in certain populations and thus are useful for population genetic studies. In this study, an HLA genetic comparison of Chimila, Wayúu, Wiwa, and Barranquilla Colombian nonrelated healthy individuals was carried out together with other populations from all over the world to trace their genetic origin, obtain a virtual transplantation list, and inform future epidemiology studies. METHODS HLA-A, -B, -DRB1, and -DQB1 alleles were sequenced using the PCR-SSOP-Luminex method to analyze the HLA genetic profile of each individual. The data obtained were subsequently processed with standard software to obtain HLA alleles, haplotype frequencies, and genetic distances compared with data from global populations to generate relatedness dendrograms and carry out a correspondence analysis. RESULTS The results obtained place the Chimila, Wayúu, and Wiwa populations phylogenetically close to the other North and South Amerindian populations included in this study. Amerindians are genetically separated from the rest of the world's populations. Chimila, Wayúu, and Wiwa present unique extended HLA haplotypes and specific alleles, such as HLA-B*48 or HLA-A*24:01, shared with Oceanian populations. CONCLUSIONS These genetic results and anthropological data support prehistorical trans-Pacific (bidirectional) contacts that contributed to the settlement of America and also suggest that the effects of ancient European gene flow cannot be discarded.
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Affiliation(s)
- Antonio Arnaiz-Villena
- Department of Immunology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
| | - Tomás Lledo
- Department of Immunology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
| | | | - Ignacio Juarez
- Department of Immunology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
| | - Christian Vaquero-Yuste
- Department of Immunology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
| | - José Manuel Martin-Villa
- Department of Immunology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
| | - Fabio Suarez-Trujillo
- Department of Immunology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain
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10
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Ross CT, Pisor AC. Perceived inequality and variability in the expression of parochial altruism. EVOLUTIONARY HUMAN SCIENCES 2025; 7:e3. [PMID: 39935444 PMCID: PMC11810521 DOI: 10.1017/ehs.2024.43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 08/23/2024] [Accepted: 08/28/2024] [Indexed: 02/13/2025] Open
Abstract
It is commonly argued that humans have generalised predispositions for within-group favouritism and between-group animus (i.e. that humans are parochially altruistic), leading to higher levels of internal conflict in societies with greater diversity. Other research, however, has questioned both the ubiquity of parochial altruism and the role of diversity per se in causing social discord. Here, we use ethnographic, social network and experimental economic game data to explore this topic in two multi-ethnic Colombian communities. We examine the extent to which Afrocolombian and Emberá residents express parochial altruism, finding appreciable variability between communities, and across individuals within communities. When present, parochial altruism appears to be driven by divergent perceptions of group-based economic need, not group identity per se. Our results suggest that diversity may be less likely to cause social discord than past work has suggested, as long as group-based inequalities in wealth, well-being and representation - that can destabilise positive inter-group relationships - are minimised.
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Affiliation(s)
- Cody T. Ross
- Max Planck Institute for Evolutionary Anthropology, Department of Human Behavior, Ecology and Culture, Leipzig, Germany
| | - Anne C. Pisor
- Max Planck Institute for Evolutionary Anthropology, Department of Human Behavior, Ecology and Culture, Leipzig, Germany
- Department of Anthropology and Social Science Research Institute, The Pennyslvania State University, University Park, PA, USA
- Department of Anthropology, Washington State University, Pullman, WA, USA
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11
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Calixto OJ, Meneses-Toro MA, Chacón PA, Acevedo-Godoy M, Robayo LC, Bello-Gualtero JM, Bautista-Molano W, Noguera V, Cortés J, Romero-Sánchez C. Allelic and haplotypic HLA analysis in patients with psoriatic arthritis: Low frequency of common alleles. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2024; 44:178-190. [PMID: 39836838 PMCID: PMC12014218 DOI: 10.7705/biomedica.7555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/18/2024] [Indexed: 01/23/2025]
Abstract
Introduction Psoriatic arthritis is a complex disease, and human leukocyte antigens (HLA) are key to its development. Latin America and, specifically, Colombia, has scarce data about patients with psoriatic arthritis. Objective To describe the genotypic, allelic and haplotypic frequency of HLA alleles in psoriatic arthritis and associate them with clinical variables. Materials and methods We conducted a retrospective study involving adult patients with psoriatic arthritis, evaluated according to CASPAR criteria, between 2012 and 2023. We included healthy donors whose HLA-A, B, C, and DR were genotyped by PCR/SSO in a Luminex 100/200 xMAP™ device. We performed an HLA comparative analysis between healthy donors and psoriatic arthritis patients. Results We included 401 healthy controls and 37 patients with psoriatic arthritis, in which we identified 46 genotypes, 75 alleles, and 32 haplotypes. The most frequent HLA were HLA-A*24 (37.1%), HLA-B*35 (20.8%), HLA-C*3 and HLA-C*7 (19.9% each), and HLADR* 4 (30%). Compared to healthy donors, the patient’s genotypic frequency was lower for HLA-A*02, HLA-A*11, HLA-B*35, HLA-DR*01, HLA-DR*07, HLA-DR*13, and HLA-DR*15 (p < 0.05), which means that even though HLA-B*35 was frequent in psoriatic arthritis, it's frequency was lower when compared to that of healthy controls. The frequency of HLA-A*24 and HLA-B*44 was different in cutaneous involvement (p < 0.05), HLA-B*40 and HLA-B*35 in joint involvement (p < 0.05), and HLA-A*26 and HLA-C*16 in extra-articular manifestations (p < 0.05). The allelic frequency of HLA-A*26:01 and HLA-C*16:01 in extra-articular manifestations was also significant. The frequency of HLA-Cw*6 was 6.7% and the allele HLA-B*27 was absent. Conclusions The HLA analysis in psoriatic arthritis showed a low frequency of HLA-C*06 and absence of HLA-B*27, different from the information reported for Caucasian population. These results also revealed other alleles of interest. Found differences could be related to the important racial mixing of our population.
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Affiliation(s)
- Omar-Javier Calixto
- Servicio de Reumatología e Inmunología, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralServicio de Reumatología e InmunologíaHospital Militar CentralBogotáColombia
- Grupo de Inmunología Clínica Aplicada, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaGrupo de Inmunología Clínica AplicadaHospital Militar CentralUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
- Grupo de Inmunología Celular y Molecular - InmuBo, Universidad El Bosque, Bogotá, D. C., ColombiaUniversidad El BosqueGrupo de Inmunología Celular y Molecular - InmuBoUniversidad El BosqueBogotá, D. C.Colombia
| | - María-Alejandra Meneses-Toro
- Servicio de Reumatología e Inmunología, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralServicio de Reumatología e InmunologíaHospital Militar CentralBogotáColombia
- Grupo de Inmunología Clínica Aplicada, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaGrupo de Inmunología Clínica AplicadaHospital Militar CentralUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
- Grupo de Inmunología Celular y Molecular - InmuBo, Universidad El Bosque, Bogotá, D. C., ColombiaUniversidad El BosqueGrupo de Inmunología Celular y Molecular - InmuBoUniversidad El BosqueBogotá, D. C.Colombia
| | - Paula Andrea Chacón
- Servicio de Dermatología, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralServicio de DermatologíaHospital Militar CentralBogotá, D. C.Colombia
| | - Mónica Acevedo-Godoy
- Grupo de Inmunología Clínica Aplicada, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaGrupo de Inmunología Clínica AplicadaHospital Militar CentralUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
- Laboratorio Clínico, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralLaboratorio ClínicoHospital Militar CentralBogotá, D. C.Colombia
| | - Luisa Constanza Robayo
- Laboratorio Clínico, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralLaboratorio ClínicoHospital Militar CentralBogotá, D. C.Colombia
| | - Juan Manuel Bello-Gualtero
- Servicio de Reumatología e Inmunología, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralServicio de Reumatología e InmunologíaHospital Militar CentralBogotáColombia
- Grupo de Inmunología Clínica Aplicada, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaGrupo de Inmunología Clínica AplicadaHospital Militar CentralUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
| | - Wilson Bautista-Molano
- Grupo de Inmunología Clínica Aplicada, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaGrupo de Inmunología Clínica AplicadaHospital Militar CentralUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
- Grupo de Inmunología Celular y Molecular - InmuBo, Universidad El Bosque, Bogotá, D. C., ColombiaUniversidad El BosqueGrupo de Inmunología Celular y Molecular - InmuBoUniversidad El BosqueBogotá, D. C.Colombia
| | - Verónica Noguera
- Servicio de Dermatología, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralServicio de DermatologíaHospital Militar CentralBogotá, D. C.Colombia
- Servicio de Dermatología, Fuerza Aérea Colombiana, Bogotá, D. C., ColombiaFuerza Aérea ColombianaServicio de DermatologíaFuerza Aérea ColombianaBogotá, D. C.Colombia
| | - Jaime Cortés
- Programa de Medicina Interna, Facultad de Medicina, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaPrograma de Medicina InternaFacultad de MedicinaUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
| | - Consuelo Romero-Sánchez
- Servicio de Reumatología e Inmunología, Hospital Militar Central, Bogotá, D. C., ColombiaHospital Militar CentralServicio de Reumatología e InmunologíaHospital Militar CentralBogotáColombia
- Grupo de Inmunología Clínica Aplicada, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, D. C., ColombiaUniversidad Militar Nueva GranadaGrupo de Inmunología Clínica AplicadaHospital Militar CentralUniversidad Militar Nueva GranadaBogotá, D. C.Colombia
- Grupo de Inmunología Celular y Molecular - InmuBo, Universidad El Bosque, Bogotá, D. C., ColombiaUniversidad El BosqueGrupo de Inmunología Celular y Molecular - InmuBoUniversidad El BosqueBogotá, D. C.Colombia
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12
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Miranda-Acuña J, Casallas-Vanegas A, McCauley J, Castro-Castro P, Amezcua L. Multiple sclerosis in Colombia: A review of the literature. Mult Scler J Exp Transl Clin 2024; 10:20552173241293921. [PMID: 39600996 PMCID: PMC11590136 DOI: 10.1177/20552173241293921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 10/09/2024] [Indexed: 11/29/2024] Open
Abstract
Background The prevalence of multiple sclerosis (MS) in Latin America is generally considered low to moderate. However, accurate data regarding MS epidemiology in Colombia is lacking. Objective This study aims to discuss the situation of MS in Colombia. Results Analysis reveals a lack of accurate data regarding MS epidemiology in Colombia, however, there have been notable improvements in diagnosis and ultimately leading to better access to treatment for MS patients. While ethnic diversity may potentially influence MS prevalence, there is currently no strong data supporting this claim. MS treatment in Colombia, focuses on early disease-modifying therapy, nevertheless, MS is considered an orphan disease in Colombia, contributing to MS patients not receiving comprehensive evaluation in MS centers. Regional efforts are ongoing to improve diagnostic access and access to treatment for MS patients. Conclusion Despite the challenges in accurately defining MS epidemiology in Colombia, an increase in neurological training, diagnostic capabilities, and access to treatment has been observed. However, the status of MS as an orphan disease in Colombia poses challenges to comprehensive care for affected individuals. Further studies are needed to elucidate risk factors and improve care conditions for MS patients in the region.
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Affiliation(s)
| | | | - Jacob McCauley
- John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, United States
| | | | - Lilyana Amezcua
- Multiple Sclerosis Comprehensive Care Center, University of Southern California, Los Angeles, CA, USA/Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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13
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Echeverría O, Angulo-Aguado M, Vela R, Calderón-Ospina C, Parra K, Contreras N, Morel A, Cabrera R, Restrepo C, Ramírez-Santana C, Ortega-Recalde O, Rojas-Quintana ME, Murcia L, Gaviria-Sabogal CC, Valero N, Fonseca-Mendoza DJ. The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing. PLoS One 2024; 19:e0306445. [PMID: 38991024 PMCID: PMC11239111 DOI: 10.1371/journal.pone.0306445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 06/18/2024] [Indexed: 07/13/2024] Open
Abstract
Clopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0; 95% CI: 1,02-24,48; p: 0,03), rs2032582 (OR: 4,41; 95% CI: 1,20-16,12; p: 0,019), and rs1045642 (OR: 3,38; 95% CI: 0,96-11,9; p: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a "surrogate" biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population.
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Affiliation(s)
- Omar Echeverría
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Mariana Angulo-Aguado
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Ricardo Vela
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Carlos Calderón-Ospina
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Katherine Parra
- Hospital Universitario Mayor—Méderi—Universidad del Rosario, Bogotá D.C., Colombia
| | - Nora Contreras
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Adrien Morel
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Rodrigo Cabrera
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Carlos Restrepo
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Carolina Ramírez-Santana
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá D.C., Colombia
| | - Oscar Ortega-Recalde
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
- Departamento de Morfología, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá D.C., Colombia
| | - Manuel Eduardo Rojas-Quintana
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá D.C., Colombia
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, United States of America
| | - Luisa Murcia
- Hospital Universitario Mayor—Méderi—Universidad del Rosario, Bogotá D.C., Colombia
| | - Cristian Camilo Gaviria-Sabogal
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Nattaly Valero
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
| | - Dora Janeth Fonseca-Mendoza
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá D.C., Colombia
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Song J, Ramírez MC, Okano JT, Service SK, de la Hoz J, Díaz-Zuluaga AM, Upegui CV, Gallago C, Arias A, Sánchez AV, Teshiba T, Sabatti C, Gur RC, Bearden CE, Escobar JI, Reus VI, Jaramillo CL, Freimer NB, Olde Loohuis LM, Blower S. Geospatial investigations in Colombia reveal variations in the distribution of mood and psychotic disorders. COMMUNICATIONS MEDICINE 2024; 4:26. [PMID: 38383761 PMCID: PMC10881503 DOI: 10.1038/s43856-024-00441-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 01/19/2024] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas. METHODS We constructed a friction surface map of Caldas and used it to calculate the travel-time to the CSJDM for 16,295 patients who had received an initial diagnosis of mood or psychotic disorder. Using a zero-inflated negative binomial regression model, we determined the relationship between travel-time and incidence, stratified by disease severity. We employed spatial scan statistics to look for patient clusters. RESULTS We show that travel-times (for driving) to the CSJDM are less than 1 h for ~50% of the population and more than 4 h for ~10%. We find a distance-decay relationship for outpatients, but not for inpatients: for every hour increase in travel-time, the number of expected outpatient cases decreases by 20% (RR = 0.80, 95% confidence interval [0.71, 0.89], p = 5.67E-05). We find nine clusters/hotspots of inpatients. CONCLUSIONS Our results reveal inequities in access to healthcare: many individuals requiring only outpatient treatment may live too far from the CSJDM to access healthcare. Targeting of resources to comprehensively identify severely ill individuals living in the observed hotspots could further address treatment inequities and enable investigations to determine factors generating these hotspots.
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Affiliation(s)
- Janet Song
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | | | - Justin T Okano
- Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Susan K Service
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Juan de la Hoz
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Ana M Díaz-Zuluaga
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | | | - Cristian Gallago
- Department of Mental Health and Human Behavior, University of Caldas, Manizales, Colombia
| | - Alejandro Arias
- Department of Psychiatry, University of Antioquía, Medellín, Colombia
| | | | - Terri Teshiba
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Chiara Sabatti
- Department of Biomedical Data Science, Stanford University, Stanford, CA, USA
| | - Ruben C Gur
- Department of Psychiatry, University of Pennsylvania School of Medicine and the Penn-CHOP Lifespan Brain Institute, Philadelphia, PA, USA
| | - Carrie E Bearden
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Javier I Escobar
- Department of Psychiatry, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Victor I Reus
- Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
| | | | - Nelson B Freimer
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Loes M Olde Loohuis
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
| | - Sally Blower
- Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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15
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Barahona-Correa JE, Herrera-Leaño NM, Bernal-Macías S, Fernández-Ávila DG. Prevalence of axial spondyloarthritis in Colombia: data from the National Health Registry 2017-2021. Clin Rheumatol 2024; 43:49-57. [PMID: 37953369 PMCID: PMC10774146 DOI: 10.1007/s10067-023-06799-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 10/13/2023] [Accepted: 10/17/2023] [Indexed: 11/14/2023]
Abstract
INTRODUCTION Registries allow ascertaining the epidemiology of chronic diseases such as axial spondyloarthritis (axSpA). The Colombian Ministry of Health has implemented a National Health Registry (SISPRO) that collects data from each medical contact in the system, which provides close to universal coverage (around 98%). OBJECTIVE To establish the 5-year prevalence of axSpA in Colombia, and to describe its demographics, using data from January 1st, 2017, to December 31st, 2021. METHODS We performed an observational, cross-sectional study using the International Statistical Classification of Diseases and Related Health Problems as search terms related to ax-SpA, based on SISPRO data. We estimated the prevalence using three approaches: (1) ankylosing spondylitis (AS) diagnoses; (2) diagnoses compatible with axSpA; and (3) diagnoses compatible with axSpA, including sacroiliitis. We calculated prevalence per 100,000 inhabitants. RESULTS Based on our three approaches, patients with a primary diagnosis compatible with ax-SpA ranged between 12,684 and 117,648, with an estimated 5-year adjusted prevalence between 26.3 and 244 cases per 100,000 inhabitants (0.03-0.2%). The male-to-female ratio ranged between 1.2:1 and 0.4:1, which was markedly skewed towards a higher prevalence in women when we included the code for sacroiliitis. We found the highest frequency of cases in the 50-54 years group. A differential prevalence was observed between different regions in our country, particularly in regions known to have European ancestors. CONCLUSION This is the first study that describes demographic characteristics of ax-SpA in Colombia and offers valuable information for stakeholders. Key Points • Using the official country-level health database, the prevalence of axSpA in Colombia ranges between 26.3 and 244 cases per 100,000 inhabitants (0.03% - 0.2%) • The prevalence of axSpA peaked among the 50-54 years patient group, suggesting an increased survival • Nations with a substantial admixture, such as Colombia, may present a differential prevalence of axSpA among regions within the country • Including the ICD-10 code for sacroiliitis (M46.1) in epidemiological studies probably overestimates the frequency of axSpA.
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Affiliation(s)
- Julián E Barahona-Correa
- Department of Internal Medicine, Hospital Universitario San Ignacio, Bogota, Colombia.
- Division of Rheumatology, Hospital Universitario San Ignacio, Bogota, Colombia.
- School of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia.
| | - Nancy M Herrera-Leaño
- Department of Internal Medicine, Hospital Universitario San Ignacio, Bogota, Colombia
- School of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia
| | - Santiago Bernal-Macías
- Department of Internal Medicine, Hospital Universitario San Ignacio, Bogota, Colombia
- Division of Rheumatology, Hospital Universitario San Ignacio, Bogota, Colombia
- School of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia
| | - Daniel G Fernández-Ávila
- Department of Internal Medicine, Hospital Universitario San Ignacio, Bogota, Colombia
- Division of Rheumatology, Hospital Universitario San Ignacio, Bogota, Colombia
- School of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia
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16
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Gutierrez-Castañeda LD, Acosta CR, Bustos MA, García DK, Bohada DP, Rodríguez R, Guerrero MI. Single Nucleotide Variants in the TLR1, TLR2 and TLR6 Genes: A Case-Control Study in a Colombian Population. Trop Med Infect Dis 2023; 8:473. [PMID: 37888601 PMCID: PMC10610572 DOI: 10.3390/tropicalmed8100473] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/09/2023] [Accepted: 08/11/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND Single nucleotide variants in toll-like receptor genes play a crucial role in leprosy susceptibility or resistance. METHODS With an epidemiology case-control study, associations between SNVs rs5743618 in TLR1, rs5743708 in TLR2, and rs5743810 in TLR6 and overall susceptibility for leprosy were estimated in 114 cases and 456 controls. Following that, stratified analysis was performed. DNA was extracted from peripheral blood. Genotyping was performed using predesigned TaqMan probes. RESULTS The A/G genotype of rs5743810 behaved as a protective factor for the development of leprosy in the codominant (OR= 0.37; 95% CI = 016-0.86, p = 0.049) and over-dominant (OR = 0.38; 95% CI = 0.16-0.88, p = 0.019) inheritance models. The A/G and A/A genotypes behaved as a protective factor (OR = 0.39; 95% CI = 0.17-0.87, p = 0.016) in the dominant model. The SNVs rs5743618 and rs5743708 showed no association with any of the models. The CGG haplotype (rs5743618-rs5743708-rs5743810) behaved as a susceptibility factor for developing leprosy (OR = 1.86; 95% CI = 1.11-3.10, p = 0.019). The latter haplotype behaved as a susceptibility factor for leprosy development in women (OR = 2.39; 95% CI = 1.21-4.82, p = 0.013). CONCLUSIONS The identified variants in the genes encoding TLRs, specifically rs5743810 in TLR6 and CGG (rs5743618-rs5743708-rs5743810) haplotypes, may somehow explain leprosy susceptibility in the studied population in a leprosy endemic region in Colombia.
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Affiliation(s)
- Luz D. Gutierrez-Castañeda
- Grupo de Ciencias Básicas en Salud (CBS)-FUCS, Instituto de Investigación, Fundación Universitaria de Ciencias de la Salud-FUCS, Bogotá 111411, Colombia
- Grupo Dermatología General, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia;
| | - Carmen R. Acosta
- Grupo Dermatología Tropical, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia;
| | - Mónica A. Bustos
- Grupo de Investigación en Enfermedades Parasitarias, Tropicales e Infecciosas (GIEPATI) Universidad de Pamplona, Pamplona 543058, Colombia; (M.A.B.); (D.P.B.); (R.R.)
| | - Diana K. García
- Grupo Dermatología General, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia;
| | - Diana P. Bohada
- Grupo de Investigación en Enfermedades Parasitarias, Tropicales e Infecciosas (GIEPATI) Universidad de Pamplona, Pamplona 543058, Colombia; (M.A.B.); (D.P.B.); (R.R.)
| | - Raúl Rodríguez
- Grupo de Investigación en Enfermedades Parasitarias, Tropicales e Infecciosas (GIEPATI) Universidad de Pamplona, Pamplona 543058, Colombia; (M.A.B.); (D.P.B.); (R.R.)
| | - Martha Inirida Guerrero
- Grupo Dermatología Tropical, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá 111511, Colombia;
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Uricoechea Patiño D, Collins A, García OJR, Santos Vecino G, Cuenca JVR, Bernal JE, Benavides Benítez E, Vergara Muñoz S, Briceño Balcázar I. High Mitochondrial Haplotype Diversity Found in Three Pre-Hispanic Groups from Colombia. Genes (Basel) 2023; 14:1853. [PMID: 37895202 PMCID: PMC10606881 DOI: 10.3390/genes14101853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 08/30/2023] [Accepted: 09/18/2023] [Indexed: 10/29/2023] Open
Abstract
The analysis of mitochondrial DNA (mtDNA) hypervariable region (HVR) sequence data from ancient human remains provides valuable insights into the genetic structure and population dynamics of ancient populations. mtDNA is particularly useful in studying ancient populations, because it is maternally inherited and has a higher mutation rate compared to nuclear DNA. To determine the genetic structure of three Colombian pre-Hispanic populations and compare them with current populations, we determined the haplotypes from human bone remains by sequencing several mitochondrial DNA segments. A wide variety of mitochondrial polymorphisms were obtained from 33 samples. Our results support a high population heterogeneity among pre-Hispanic populations in Colombia.
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Affiliation(s)
- Daniel Uricoechea Patiño
- Doctoral Program in Biosciences, Human Genetics Group, Faculty of Medicine, University of La Sabana, Chía 250001, Colombia;
| | - Andrew Collins
- Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK;
| | | | - Gustavo Santos Vecino
- Department of Anthropology, Faculty of Social and Human Science, Universidad de Antioquia, Medellín 050010, Colombia;
| | | | - Jaime E. Bernal
- Faculty of Medicine, University of Sinú, Cartagena de Indias 130011, Colombia; (J.E.B.); (E.B.B.); (S.V.M.)
| | - Escilda Benavides Benítez
- Faculty of Medicine, University of Sinú, Cartagena de Indias 130011, Colombia; (J.E.B.); (E.B.B.); (S.V.M.)
| | - Saray Vergara Muñoz
- Faculty of Medicine, University of Sinú, Cartagena de Indias 130011, Colombia; (J.E.B.); (E.B.B.); (S.V.M.)
| | - Ignacio Briceño Balcázar
- Doctoral Program in Biosciences, Human Genetics Group, Faculty of Medicine, University of La Sabana, Chía 250001, Colombia;
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Castillo A, Rondón F, Mantilla G, Gusmão L, Simão F. Maternal ancestry and lineages diversity of the Santander population from Colombia. Forensic Sci Res 2023; 8:241-248. [PMID: 38221971 PMCID: PMC10785602 DOI: 10.1093/fsr/owad032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/20/2023] [Indexed: 01/16/2024] Open
Abstract
Santander, located in the Andean region of Colombia, is one of the 32 departments of the country. Its population was shaped by intercontinental admixture between autochthonous native Americans, European settlers, and African slaves. To establish forensic databases of haplotype frequencies, the evaluation of population substructure is crucial to capture the genetic diversity in admixed populations. Total control region mitochondrial deoxyribonucleic acid haplotypes were determined for 204 individuals born in the seven provinces across the department. The maternal native heritage is highly preserved in Santander genetic background, with 90% of the haplotypes belonging to haplogroups inside A2, B4, C1, and D. Most native lineages are found broadly across the American continent, while some sub-branches are concentrated in Central America and north South America. Subtle European (6%) and African (4%) input was detected. In pairwise comparisons between provinces, relatively high FST values were found in some cases, although not statistically significant. Nonetheless, when provinces were grouped according to the principal component analysis results, significant differences were detected between groups. The database on mitochondrial deoxyribonucleic acid control region haplotype frequencies established here can be further used for populational and forensic purposes.
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Affiliation(s)
- Adriana Castillo
- Department of Basic Sciences, Genetics Laboratory, Industrial University of Santander, 680002, Bucaramanga, Colombia
| | - Fernando Rondón
- Department of Basic Sciences, Genetics Laboratory, Industrial University of Santander, 680002, Bucaramanga, Colombia
| | - Gerardo Mantilla
- Department of Basic Sciences, Genetics Laboratory, Industrial University of Santander, 680002, Bucaramanga, Colombia
| | - Leonor Gusmão
- DNA Diagnostic Laboratory, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, 20550-900, Rio de Janeiro, Brazil
| | - Filipa Simão
- DNA Diagnostic Laboratory, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, 20550-900, Rio de Janeiro, Brazil
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Vargas-Hernández DA, Uscategui-Ruiz AC, De Avila J, Romero-Sánchez C. Differences in the distribution of hemoglobin variants according to the geographic regions in a Colombian population. Hematol Transfus Cell Ther 2023; 45 Suppl 2:S140-S147. [PMID: 36764860 PMCID: PMC10433307 DOI: 10.1016/j.htct.2022.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 07/24/2022] [Accepted: 11/24/2022] [Indexed: 02/01/2023] Open
Abstract
INTRODUCTION Colombia has been subject to intense genetic and cultural currents due to its geographical location. Hemoglobinopathies are the most common recessive diseases found worldwide and represent an important public health problem, according to the region and ancestry of each country. OBJECTIVES To evaluate the frequency of hemoglobin variants according to the geographical region in a population group adjusted to sex and age in Colombia. METHODS This was a descriptive retrospective study of hemoglobin variants performed by electrophoresis in patients treated at and/or referred to specialized care institutions in Bogota, Colombia between January 2009 and December 2020. RESULTS A total of 2,224 results were analyzed, 48.4% male and 51.5% female; 63.3% of patients were without alterations, 14.3% presented with thalassemia, 17.3%, HbS, 2.3%, HbS/C, 1.8%, HbC, 0.5%, HbE and 0.5% persistent HbF, with HbS being more prevalent in males (p = 0.005). When assessing the geographical regions of Colombia, a higher prevalence of HbS was found in the Pacific (p = 0.005) and Caribbean regions, while Thalassemia and HbS were more prevalent in the Andean and Orinoquia regions, and it was rare to find any hemoglobinopathies (p = 0.0001) in the Amazonian region. CONCLUSIONS The main hemoglobinopathies found in Colombia are HbS, predominantly in males, and Thalassemia. The distribution of hemoglobinopathies in different geographical regions of Colombia is influenced by ancestry.
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Affiliation(s)
- Diego A Vargas-Hernández
- Universidad Militar Nueva Granada, Medical School, Bogotá, Colombia; Hospital Militar Central, Department of Internal Medicine, Bogota, Colombia.
| | - Adriana Catalina Uscategui-Ruiz
- Universidad Militar Nueva Granada, Medical School, Bogotá, Colombia; Hospital Militar Central, Department of Internal Medicine, Bogota, Colombia
| | - Juliette De Avila
- Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia
| | - Consuelo Romero-Sánchez
- Universidad Militar Nueva Granada, Medical School, Bogotá, Colombia; Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia.
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20
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Couto-Silva CM, Nunes K, Venturini G, Araújo Castro e Silva M, Pereira LV, Comas D, Pereira A, Hünemeier T. Indigenous people from Amazon show genetic signatures of pathogen-driven selection. SCIENCE ADVANCES 2023; 9:eabo0234. [PMID: 36888716 PMCID: PMC9995071 DOI: 10.1126/sciadv.abo0234] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 02/08/2023] [Indexed: 06/18/2023]
Abstract
Ecological conditions in the Amazon rainforests are historically favorable for the transmission of numerous tropical diseases, especially vector-borne diseases. The high diversity of pathogens likely contributes to the strong selective pressures for human survival and reproduction in this region. However, the genetic basis of human adaptation to this complex ecosystem remains unclear. This study investigates the possible footprints of genetic adaptation to the Amazon rainforest environment by analyzing the genomic data of 19 native populations. The results based on genomic and functional analysis showed an intense signal of natural selection in a set of genes related to Trypanosoma cruzi infection, which is the pathogen responsible for Chagas disease, a neglected tropical parasitic disease native to the Americas that is currently spreading worldwide.
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Affiliation(s)
- Cainã M. Couto-Silva
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, 05508090, Brazil
| | - Kelly Nunes
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, 05508090, Brazil
| | - Gabriela Venturini
- Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Marcos Araújo Castro e Silva
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, 05508090, Brazil
- Institut de Biologia Evolutiva, Departament de Medicina i Ciències de la Vida, Universitat Pompeu Fabra, Barcelona 08003, Spain
| | - Lygia V. Pereira
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, 05508090, Brazil
| | - David Comas
- Institut de Biologia Evolutiva, Departament de Medicina i Ciències de la Vida, Universitat Pompeu Fabra, Barcelona 08003, Spain
| | - Alexandre Pereira
- Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Tábita Hünemeier
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, 05508090, Brazil
- Institut de Biologia Evolutiva (CSIC/Universitat Pompeu Fabra), Barcelona 08003, Spain
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Montero-Ovalle W, Sanabria-Salas MC, Mesa-López de Mesa J, Varela-Ramírez R, Segura-Moreno YY, Sánchez-Villalobos SA, Nuñez-Lemus M, Serrano ML. Determination of TMPRSS2-ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis. Cell Biol Int 2023; 47:1017-1030. [PMID: 36740223 DOI: 10.1002/cbin.12000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/30/2022] [Accepted: 01/21/2023] [Indexed: 02/07/2023]
Abstract
Prostate cancer (PCa) is one of cancer with of the highest incidence and mortality worldwide. Current disease prognostic markers do not differentiate aggressive from indolent PCa with sufficient certainty, and characterization by molecular subtypes has been sought to allow a better classification. TMPRSS2-ERG, SPOP, FOXA1, and IDH1 molecular subtypes have been described, but the association of these subtypes with prognosis in PCa is unclear; their frequency in Colombian patients is also unknown. Formalin-fixed and paraffin-embedded samples of radical prostatectomy from 112 patients with PCa were used. The TMPRSS2-ERG subtype was assessed with fluorescent in situ hybridization. The mutations in SPOP, FOXA1, and IDH1 in hot-spot regions were evaluated using Sanger sequencing. Fusion was detected in 71 patients (63.4%). No statistically significant differences were found between the state of fusion and the variables analyzed. In the 41 fusion-negative cases (36.6%), two patients (4.9%) had missense mutations in SPOP (p.F102C and p.F133L), representing a 1.8% of the overall cohort. The low frequency of this subtype in Colombians could be explained by the reported variability in the frequency of these mutations according to the population (5%-20%). No mutations were found in FOXA1 in the cases analyzed. The synonym SNP rs11554137 IDH1105GGT was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.
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Affiliation(s)
- Wendy Montero-Ovalle
- Cancer Biology Research Group, Instituto Nacional de Cancerología, Bogotá, Colombia.,Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia, Bogotá, Colombia
| | | | | | - Rodolfo Varela-Ramírez
- Department of Oncological Urology, Instituto Nacional de Cancerología, Bogotá, Colombia.,Department of Surgery, Faculty of Medicine Universidad Nacional de Colombia, Bogotá, Colombia
| | | | | | - Marcela Nuñez-Lemus
- Research Support and Monitoring Group, Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Martha L Serrano
- Cancer Biology Research Group, Instituto Nacional de Cancerología, Bogotá, Colombia.,Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia, Bogotá, Colombia
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22
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Polanía D, Reyes-Guanes J, Rojas-Carabali W, Pardo-Pizza D, Barraquer-Lopez D, Cifuentes-González C, Neira-Segura N, de-la-Torre A. A new look into uveitis in Colombia: changes in distribution patterns and clinical characteristics over the last 25 years. Graefes Arch Clin Exp Ophthalmol 2023; 261:561-573. [PMID: 35994112 PMCID: PMC9836979 DOI: 10.1007/s00417-022-05796-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 07/20/2022] [Accepted: 08/01/2022] [Indexed: 01/17/2023] Open
Abstract
PURPOSE To describe the distribution patterns and clinical characteristics of patients diagnosed with uveitis at a specialized uveitis center in Bogotá, Colombia, from 2013 to 2021 and compare these patterns with the previously reported between 1996 and 2006. METHODS We performed an observational descriptive cross-sectional study systematically reviewing clinical records of patients attending between 2013 and 2021. Data were analyzed and compared with previous reports. RESULTS Of the 489 patients with uveitis, 310 were females (63.4%). The mean age of onset was 38.7, with a range between 1 and 83 years. Bilateral (52.8%), anterior (45.8%), non-granulomatous (90.8%), and recurrent (47.6%) were the most common types of uveitis found in our population sample. The most common cause of uveitis in this study was idiopathic, followed by toxoplasmosis and HLA-B27 + associated uveitis, which differs from the previous Colombian study where ocular toxoplasmosis was the most frequent cause. This highlights a significant shift from infectious etiologies to more immune-mediated processes as the cause of uveitis in Colombia nowadays. CONCLUSION The results of this study provide a comparison between the clinical patterns of presentation of uveitis from 1996 to 2006 and the patterns observed from 2013 to 2021, enhancing awareness about the changing dynamics of uveitis in Colombia to guide a better understanding of the diagnosis, classification, and correlation with other systemic conditions of the disease.
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Affiliation(s)
- Diego Polanía
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
- Ophthalmology Interest Group, Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - Juliana Reyes-Guanes
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - William Rojas-Carabali
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - Daniella Pardo-Pizza
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
- Ophthalmology Interest Group, Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - Doménico Barraquer-Lopez
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
- Ophthalmology Interest Group, Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - Carlos Cifuentes-González
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - Natalia Neira-Segura
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia
| | - Alejandra de-la-Torre
- Neuroscience Research Group (NEUROS), Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia.
- Ophthalmology Interest Group, Escuela de Medicina Y Ciencias de La Salud, Universidad del Rosario, Bogotá, Colombia.
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Parada-Márquez JF, Maldonado-Rodriguez ND, Triana-Fonseca P, Contreras-Bravo NC, Calderón-Ospina CA, Restrepo CM, Morel A, Ortega-Recalde OJ, Silgado-Guzmán DF, Angulo-Aguado M, Fonseca-Mendoza DJ. Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations. Front Pharmacol 2023; 14:1047854. [PMID: 37021041 PMCID: PMC10069477 DOI: 10.3389/fphar.2023.1047854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 03/06/2023] [Indexed: 04/07/2023] Open
Abstract
Background: Genetic interindividual variability is associated with adverse drug reactions (ADRs) and affects the response to common drugs used in anesthesia. Despite their importance, these variants remain largely underexplored in Latin-American countries. This study describes rare and common variants found in genes related to metabolism of analgesic and anaesthetic drug in the Colombian population. Methods: We conducted a study that included 625 Colombian healthy individuals. We generated a subset of 14 genes implicated in metabolic pathways of common medications used in anesthesia and assessed them by whole-exome sequencing (WES). Variants were filtered using two pipelines: A) novel or rare (minor allele frequency-MAF <1%) variants including missense, loss-of-function (LoF, e.g., frameshift, nonsense), and splice site variants with potential deleterious effect and B) clinically validated variants described in the PharmGKB (categories 1, 2 and 3) and/or ClinVar databases. For rare and novel missense variants, we applied an optimized prediction framework (OPF) to assess the functional impact of pharmacogenetic variants. Allelic, genotypic frequencies and Hardy-Weinberg equilibrium were calculated. We compare our allelic frequencies with these from populations described in the gnomAD database. Results: Our study identified 148 molecular variants potentially related to variability in the therapeutic response to 14 drugs commonly used in anesthesiology. 83.1% of them correspond to rare and novel missense variants classified as pathogenic according to the pharmacogenetic optimized prediction framework, 5.4% were loss-of-function (LoF), 2.7% led to potential splicing alterations and 8.8% were assigned as actionable or informative pharmacogenetic variants. Novel variants were confirmed by Sanger sequencing. Allelic frequency comparison showed that the Colombian population has a unique pharmacogenomic profile for anesthesia drugs with some allele frequencies different from other populations. Conclusion: Our results demonstrated high allelic heterogeneity among the analyzed sampled, enriched by rare (91.2%) variants in pharmacogenes related to common drugs used in anesthesia. The clinical implications of these results highlight the importance of implementation of next-generation sequencing data into pharmacogenomic approaches and personalized medicine.
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Affiliation(s)
| | | | - Paula Triana-Fonseca
- Department of Molecular Diagnosis, Genética Molecular de Colombia SAS, Bogotá, Colombia
| | - Nora Constanza Contreras-Bravo
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
| | - Carlos Alberto Calderón-Ospina
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
| | - Carlos M. Restrepo
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
| | - Adrien Morel
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
| | - Oscar Javier Ortega-Recalde
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
| | | | - Mariana Angulo-Aguado
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
- *Correspondence: Mariana Angulo-Aguado, ; Dora Janeth Fonseca-Mendoza,
| | - Dora Janeth Fonseca-Mendoza
- School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia
- *Correspondence: Mariana Angulo-Aguado, ; Dora Janeth Fonseca-Mendoza,
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Sickle Cell Trait, Clinical Manifestations and Outcomes: A Cross-Sectional Study in Colombia: Increasing Rate of Symptomatic Subjects Living in High Altitude. Mediterr J Hematol Infect Dis 2023; 15:e2023015. [PMID: 36908870 PMCID: PMC10000961 DOI: 10.4084/mjhid.2023.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 02/15/2023] [Indexed: 03/05/2023] Open
Abstract
Background Sickle cell trait (SCT) is an autosomal recessive blood disorder in which patients are heterozygous carriers for hemoglobin S (HbAS) and are usually asymptomatic. We performed a descriptive analysis of clinical manifestations and outcomes associated with SCT. Methods This was a descriptive, cross-sectional study that included patients with SCT from 2014 to 2020 at Hospital Militar Central, the reference center of the Military forces in Bogota, Colombia. Results Of 647 hemoglobin electrophoresis analyzed, we identified 51 patients with SCT, including 43 males (84.3%) and eight females (15.7%), with a median age of 22 years (IQR 15-36 years). Of these, 28 (54.8%) were Afro-Colombian, 23 (45.1%) were Colombian mestizos, and 31/51 (60.8%) of patients were active military members. Twenty-four patients (47.1%) were asymptomatic, and Twenty-seven patients (52.9%) were symptomatic (systemic complications); Most of the patients who presented symptoms were active military members of the Colombian military forces. Splenic complications were the most important (85.2%), p=0.0005, and there was a wide spectrum of splenic complications. In addition, we found significant elevations in leukocytes, bilirubin, LDH, and CRP. Eighteen patients (66.7%) received medical management, five (18.5%) required splenectomy, and only 5.9% of patients were sent for genetic counseling. Conclusions Military Personnel is a population with a high risk of developing symptoms, and splenic complications were the most relevant in symptomatic patients. Most patients received medical treatment, and 18.5% of patients required splenectomy. Our results reflect the absence of redirection of these patients to genetic counseling.
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Association of the rs2111234, rs3135499, rs8057341 polymorphisms in the NOD2 gene with leprosy: A case-control study in the Norte de Santander, Colombia population. PLoS One 2023; 18:e0281553. [PMID: 36877680 PMCID: PMC9987820 DOI: 10.1371/journal.pone.0281553] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 01/26/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The development of leprosy involves several factors, including the causative agent, the individual host's immune response, environmental factors, and the genetic background of the host. Specifically, the host's innate immune response, encoded by genes, determines their susceptibility to developing leprosy post-infection. Polymorphic variants in the nucleotide-binding oligomerization domain 2 (NOD2) gene are associated with leprosy among populations in a variety of endemic areas around the world. Colombia, a country located in the tropical zone, has several leprosy-endemic regions, including Norte de Santander. The aim of this study was to analyze the rs7194886, rs2111234, rs3135499, and rs8057341 single nucleotide polymorphisms (SNPs) in the NOD2 gene using a case-control study to determine whether they confer greater or lesser susceptibility to the development of leprosy. METHODOLOGY The TaqMan qPCR amplification system was used for SNPs detection. FINDINGS An association between the A-rs8057341 SNP (p = 0,006286) and resistance to leprosy was found. However, the rs3135499 (p = 0,9063) and rs2111234 (p = 0.1492) were not found to be associated with leprosy susceptibility. In addition, the rs7194886 SNP was not found to be in Hardy-Weinberg equilibrium (HWE) in the study population. The GAG haplotype, consisting of SNPs rs2111234-G, rs3135499-A, and rs8057341G, acts as a susceptibility factor for the development of leprosy in women. SNPs rs3135499 and rs8057341 are functionally related to decreased NOD2 expression according to an in-silico analysis. CONCLUSIONS The SNPs rs8057341-A was related with resistance to leprosy and the haplotype rs2111234-G, rs3135499-A and rs8057341-G SNPs was related with susceptibility in the Norte de Santander Colombia, studied population.
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Rey-Vargas L, Bejarano-Rivera LM, Mejia-Henao JC, Sua LF, Bastidas-Andrade JF, Ossa CA, Gutiérrez-Castañeda LD, Fejerman L, Sanabria-Salas MC, Serrano-Gómez SJ. Association of genetic ancestry with HER2, GRB7 AND estrogen receptor expression among Colombian women with breast cancer. Front Oncol 2022; 12:989761. [PMID: 36620598 PMCID: PMC9815522 DOI: 10.3389/fonc.2022.989761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
Background Our previous study reported higher mRNA levels of the human epidermal growth factor receptor 2 (HER2)-amplicon genes ERBB2 and GRB7 in estrogen receptor (ER)-positive breast cancer patients with relatively high Indigenous American (IA) ancestry from Colombia. Even though the protein expression of HER2 and GRB7 is highly correlated, they may also express independently, an event that could change the patients' prognosis. In this study, we aimed to explore the differences in ER, HER2 and GRB7 protein expression according to genetic ancestry, to further assess the clinical implications of this association. Methods We estimated genetic ancestry from non-tumoral breast tissue DNA and assessed tumoral protein expression of ER, HER2, and GRB7 by immunohistochemistry in a cohort of Colombian patients from different health institutions. We used binomial and multinomial logistic regression models to test the association between genetic ancestry and protein expression. Kaplan-Meier and log-rank tests were used to evaluate the effect of HER2/GRB7 co-expression on patients' survival. Results Our results show that patients with higher IA ancestry have higher odds of having HER2+/GRB7- breast tumors, compared to the HER2-/GRB7- subtype, and this association seems to be stronger among ER-positive tumors (ER+/HER2+/GRB7-: OR=3.04, 95% CI, 1.47-6.37, p<0.05). However, in the multivariate model this association was attenuated (OR=1.80, 95% CI, 0.72-4.44, p=0.19). On the other hand, it was observed that having a higher European ancestry patients presented lower odds of ER+/HER2+/GRB7- breast tumors, this association remained significant in the multivariate model (OR=0.36, 95% CI, 0.13 - 0.93, p= 0.0395). The survival analysis according to HER2/GRB7 co-expression did not show statistically significant differences in the overall survival and recurrence-free survival. Conclusions Our results suggest that Colombian patients with higher IA ancestry and a lower European fraction have higher odds of ER+/HER2+/GRB7- tumors compared to ER+/HER2-/GRB7- disease. However, this association does not seem to be associated with patients' overall or recurrence-free survival.
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Affiliation(s)
- Laura Rey-Vargas
- Cancer Biology Research Group, National Cancer Institute of Colombia, Bogotá, Colombia,Doctoral Program in Biological Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Juan Carlos Mejia-Henao
- Oncological Pathology Research Group, National Cancer Institute of Colombia, Bogotá, Colombia
| | - Luz F. Sua
- Department of Pathology and Laboratory Medicine, Fundación Valle del Lili, and Faculty of Health Sciences, Universidad ICESI, Cali, Colombia
| | | | | | - Luz Dary Gutiérrez-Castañeda
- Research Institute, Group of Basic Sciences in Health (CBS), Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia
| | - Laura Fejerman
- Department of Public Health Sciences and Comprehensive Cancer Center, University of California Davis, Davis, CA, United States
| | | | - Silvia J. Serrano-Gómez
- Cancer Biology Research Group, National Cancer Institute of Colombia, Bogotá, Colombia,Research support and follow-up group, National Cancer Institute of Colombia, Bogotá, Colombia,*Correspondence: Silvia J. Serrano-Gómez,
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Guevara-Tique AA, Torres RC, Bravo MM, Carvajal Carmona LG, Echeverry de Polanco MM, Bohórquez ME, Torres J. Recombination events drives the emergence of Colombian Helicobacter pylori subpopulations with self-identity ancestry. Virulence 2022; 13:1146-1160. [PMID: 35838227 PMCID: PMC9291697 DOI: 10.1080/21505594.2022.2095737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Helicobacter pylori have coevolved with mankind since its origins, adapting to different human groups. In America, H. pylori has evolved into several subpopulations. We analysed the genome of 154 Colombian strains along with 1,091 strains from worldwide populations to discern the ancestry and adaption to Colombian people. Population structure and ancestry was inferred with FineStructure and ChromoPainter. Phylogenetic relationship and the relative effect of recombination were analysing the core SNPs. Also, a Fst index was calculated to identify the gene variants with the strongest fixation in the Colombian subpopulations compared to their parent population hspSWEurope. FineStructure allowed the identification of two Colombian subpopulations, the previously described hspSWEuropeColombia and a novel subpopulation named hspColombia, that included three subgroups following their geographic origin. Colombian subpopulations represent an admixture of European, African and Indigenous ancestry; although some genomes showed a high proportion of self identity, suggesting an advanced adaption to these mestizo Colombian groups. We found that recombination is more important that punctual mutations in H. pylori genome diversity, 13.9 more important in hspSWEurope, 12.5 in hspSWEColombia and 10.5 in hspColombia, reflecting the divergence of these subpopulations. Fst analysis identified 82 SNPs fixed in 26 genes of the hspColombia subpopulation that encode for outer membrane and central metabolism proteins. Strongest fixation indexes were identified in genes encoding HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that H. pylori has evolved in Colombia to give rise to subpopulations with a self identity ancestry, reflected in allele changes on genes encoding for outer membrane proteins.
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Affiliation(s)
- Alix A Guevara-Tique
- Grupo de Investigación en Citogenética, Filogenia y Evolución de Poblaciones, Departamento de Ciencias y Ciencias de la Salud, Universidad del Tolima, Tolima, Colombia
| | - Roberto C Torres
- The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
| | - Maria M Bravo
- Laboratorio de Inmunología, Instituto Nacional de Cancerología, Bogotá, D. C., Colombia
| | - Luis G Carvajal Carmona
- Genome Center, Department of Biochemistry and Molecular Medicine, School of Medicine-University of California, Davis, California, USA
| | - María M Echeverry de Polanco
- Grupo de Investigación en Citogenética, Filogenia y Evolución de Poblaciones, Departamento de Ciencias y Ciencias de la Salud, Universidad del Tolima, Tolima, Colombia
| | - Mabel E Bohórquez
- Grupo de Investigación en Citogenética, Filogenia y Evolución de Poblaciones, Departamento de Ciencias y Ciencias de la Salud, Universidad del Tolima, Tolima, Colombia.,Medicine Program, Department of Health Sciences, Tolima University, Tolima, Colombia
| | - Javier Torres
- c Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatria, Instituto Mexicano del Seguro Social, México
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Herrera M, Keynan Y, McLaren PJ, Isaza JP, Abrenica B, López L, Marin D, Rueda ZV. Gene expression profiling identifies candidate biomarkers for new latent tuberculosis infections. A cohort study. PLoS One 2022; 17:e0274257. [PMID: 36170228 PMCID: PMC9518923 DOI: 10.1371/journal.pone.0274257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/25/2022] [Indexed: 11/25/2022] Open
Abstract
Objective To determine the gene expression profile in individuals with new latent tuberculosis infection (LTBI), and to compare them with people with active tuberculosis (TB) and those exposed to TB but not infected. Design A prospective cohort study. Recruitment and follow-up were conducted between September 2016 to December 2018. Gene expression and data processing and analysis from April 2019 to April 2021. Setting Two male Colombian prisons. Participants 15 new tuberculin skin test (TST) converters (negative TST at baseline that became positive during follow-up), 11 people that continued with a negative TST after two years of follow-up, and 10 people with pulmonary ATB. Main outcome measures Gene expression profile using RNA sequencing from PBMC samples. The differential expression was assessed using the DESeq2 package in Bioconductor. Genes with |logFC| >1.0 and an adjusted p-value < 0.1 were differentially expressed. We analyzed the differences in the enrichment of KEGG pathways in each group using InterMiner. Results The gene expression was affected by the time of incarceration. We identified group-specific differentially expressed genes between the groups: 289 genes in people with a new LTBI and short incarceration (less than three months of incarceration), 117 in those with LTBI and long incarceration (one or more years of incarceration), 26 in ATB, and 276 in the exposed but non-infected individuals. Four pathways encompassed the largest number of down and up-regulated genes among individuals with LTBI and short incarceration: cytokine signaling, signal transduction, neutrophil degranulation, and innate immune system. In individuals with LTBI and long incarceration, the only enriched pathway within up-regulated genes was Emi1 phosphorylation. Conclusions Recent infection with MTB is associated with an identifiable RNA pattern related to innate immune system pathways that can be used to prioritize LTBI treatment for those at greatest risk for developing active TB.
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Affiliation(s)
- Mariana Herrera
- Departments of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Canada
- Doctorado en Epidemiologia, Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, Colombia
| | - Yoav Keynan
- Departments of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Paul J. McLaren
- Departments of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Canada
- JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Juan Pablo Isaza
- Facultad de Medicina, Universidad Pontificia Bolivariana, Medellín, Colombia
| | - Bernard Abrenica
- JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Lucelly López
- Facultad de Medicina, Universidad Pontificia Bolivariana, Medellín, Colombia
| | - Diana Marin
- Facultad de Medicina, Universidad Pontificia Bolivariana, Medellín, Colombia
| | - Zulma Vanessa Rueda
- Departments of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Canada
- Facultad de Medicina, Universidad Pontificia Bolivariana, Medellín, Colombia
- * E-mail:
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Analysis of Ana/Dfs70 Pattern in a Large Cohort of Autoimmune/Autoinflammatory Diseases Compared with First Degree Relatives and Healthy Controls Evaluated from Colombia. Diagnostics (Basel) 2022; 12:diagnostics12092181. [PMID: 36140581 PMCID: PMC9498280 DOI: 10.3390/diagnostics12092181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022] Open
Abstract
Background: The presence of Antinuclear antibodies/Dense Fine Speckled 70 (ANA/DFS70) has been proposed as a negative biomarker in the process of exclusion of systemic autoimmune/autoinflammatory rheumatic diseases (SARD). The purpose was to evaluate and characterize ANA/DFS70 patients in a large Colombian population with SARD; rheumatoid arthritis (RA), Psoriasis (PsO), Undifferentiated connective tissue disease (UCTD), first-degree relatives of (FDR), and healthy controls (HC). Methods: ANA determination was performed using indirect immunofluorescence. Samples with positive dense fine granular staining in the nucleoplasm of the interphase cell (AC2) fluorescence were confirmed with CytoBead/ANA and ANA/modified (Knocked out for the PSPI1 gen). Results: 530 mestizo Colombian participants were included. ANA/DFS70 antibody positivity in the whole group was 2.3%, and 0.8% in SARD; no RA patients were positive. ANA/DFS70 positives in UCTD were three women; the average time of evolution of the disease was 9.4 years. The most frequent clinical findings were arthralgias, non-erosive arthritis, and Raynaud’s phenomenon. The PsO positive was a woman with C-reactive protein (CRP) positivity and a negative erythrocyte sedimentation rate (ESR) without any other positive autoantibody or extracutaneous manifestation. FDR and HC positives were 7/8 women. All were negative for other autoantibodies. Conclusions: ANA/DFS70 autoantibodies were present in Colombian patients with SARD at a shallow frequency, they were more prevalent in healthy individuals.
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Hurtado C, Rojas-Gualdrón DF, Urrego R, Cashman K, Vásquez-Trespalacios EM, Díaz-Coronado JC, Rojas M, Jenks S, Vásquez G, Sanz I. Altered B cell phenotype and CD27+ memory B cells are associated with clinical features and environmental exposure in Colombian systemic lupus erythematosus patients. Front Med (Lausanne) 2022; 9:950452. [PMID: 36148466 PMCID: PMC9485945 DOI: 10.3389/fmed.2022.950452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 08/15/2022] [Indexed: 12/02/2022] Open
Abstract
Background B lymphocytes are dysregulated in Systemic Lupus Erythematosus (SLE) including the expansion of extrafollicular B cells in patients with SLE of African American ancestry, which is associated with disease activity and nephritis. The population of Colombia has a mixture of European, Native American, and African ancestry. It is not known if Colombian patients have the same B cell distributions described previously and if they are associated with disease activity, clinical manifestations, and environmental exposures. Objective To characterize B cell phenotype in a group of Colombian Systemic Lupus Erythematosus patients with mixed ancestry and determine possible associations with disease activity, clinical manifestations, the DNA methylation status of the IFI44L gene and environmental exposures. Materials and methods Forty SLE patients and 17 healthy controls were recruited. Cryopreserved peripheral B lymphocytes were analyzed by multiparameter flow cytometry, and the DNA methylation status of the gene IFI44L was evaluated in resting Naive B cells (rNAV). Results Extrafollicular active Naive (aNAV) and Double Negative type 2, DN2 (CD27− IgD− CD21− CD11c+) B cells were expanded in severe active patients and were associated with nephritis. Patients had hypomethylation of the IFI44L gene in rNAV cells. Regarding environmental exposure, patients occupationally exposed to organic solvents had increased memory CD27+ cells (SWM). Conclusion aNAV and DN2 extrafollicular cells showed significant clinical associations in Colombian SLE patients, suggesting a relevant role in the disease’s pathophysiology. Hypomethylation of the IFI44L gene in resting Naive B cells suggests that epigenetic changes are established at exceedingly early stages of B cell ontogeny. Also, an alteration in SWM memory cells was observed for the first time in patients exposed to organic solvents. This opens different clinical and basic research possibilities to corroborate these findings and deepen the knowledge of the relationship between environmental exposure and SLE.
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Affiliation(s)
- Carolina Hurtado
- School of Medicine, Universidad CES, Medellín, Colombia
- School of Graduate Studies, Universidad CES, Medellín, Colombia
| | | | - Rodrigo Urrego
- Group INCA-CES, School of Veterinary Medicine and Zootechnic, Universidad CES, Medellín, Colombia
| | - Kevin Cashman
- Lowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, GA, United States
| | | | - Juan Camilo Díaz-Coronado
- School of Medicine, Universidad CES, Medellín, Colombia
- Group of Clinical Information, Artmedica IPS, Medellín, Colombia
| | - Mauricio Rojas
- Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia
- Unidad de Citometría de Flujo, Universidad de Antioquia, Medellín, Colombia
| | - Scott Jenks
- Lowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, GA, United States
| | - Gloria Vásquez
- Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia
| | - Ignacio Sanz
- Lowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, GA, United States
- *Correspondence: Ignacio Sanz,
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Silgado-Guzmán DF, Angulo-Aguado M, Morel A, Niño-Orrego MJ, Ruiz-Torres DA, Contreras Bravo NC, Restrepo CM, Ortega-Recalde O, Fonseca-Mendoza DJ. Characterization of ADME Gene Variation in Colombian Population by Exome Sequencing. Front Pharmacol 2022; 13:931531. [PMID: 35846994 PMCID: PMC9280300 DOI: 10.3389/fphar.2022.931531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/08/2022] [Indexed: 11/18/2022] Open
Abstract
In genes related to drug pharmacokinetics, molecular variations determine interindividual variability in the therapeutic efficacy and adverse drug reactions. The assessment of single-nucleotide variants (SNVs) is used with growing frequency in pharmacogenetic practice, and recently, high-throughput genomic analyses obtained through next-generation sequencing (NGS) have been recognized as powerful tools to identify common, rare and novel variants. These genetic profiles remain underexplored in Latin-American populations, including Colombia. In this study, we investigated the variability of 35 genes included in the ADME core panel (absorption, distribution, metabolism, and excretion) by whole-exome sequencing (WES) of 509 unrelated Colombian individuals with no previous reports of adverse drug reactions. Rare variants were filtered according to the minor allele frequencies (MAF) <1% and potential deleterious consequences. The functional impact of novel and rare missense variants was assessed using an optimized framework for pharmacogenetic variants. Bioinformatic analyses included the identification of clinically validated variants described in PharmGKB and ClinVar databases. Ancestry from WES data was inferred using the R package EthSEQ v2.1.4. Allelic frequencies were compared to other populations reported in the public gnomAD database. Our analysis revealed that rare missense pharmacogenetic variants were 2.1 times more frequent than common variants with 121 variants predicted as potentially deleterious. Rare loss of function (LoF) variants were identified in 65.7% of evaluated genes. Regarding variants with clinical pharmacogenetic effect, our study revealed 89 sequence variations in 28 genes represented by missense (62%), synonymous (22.5%), splice site (11.2%), and indels (3.4%). In this group, ABCB1, ABCC2, CY2B6, CYP2D6, DPYD, NAT2, SLC22A1, and UGTB2B7, are the most polymorphic genes. NAT2, CYP2B6 and DPYD metabolizer phenotypes demonstrated the highest variability. Ancestry analysis indicated admixture in 73% of the population. Allelic frequencies exhibit significant differences with other Latin-American populations, highlighting the importance of pharmacogenomic studies in populations of different ethnicities. Altogether, our data revealed that rare variants are an important source of variability in pharmacogenes involved in the pharmacokinetics of drugs and likely account for the unexplained interindividual variability in drug response. These findings provide evidence of the utility of WES for pharmacogenomic testing and into clinical practice.
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Affiliation(s)
| | - Mariana Angulo-Aguado
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Adrien Morel
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - María José Niño-Orrego
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Daniel-Armando Ruiz-Torres
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Nora Constanza Contreras Bravo
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Carlos Martin Restrepo
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Oscar Ortega-Recalde
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
- *Correspondence: Oscar Ortega-Recalde, ; Dora Janeth Fonseca-Mendoza,
| | - Dora Janeth Fonseca-Mendoza
- Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
- *Correspondence: Oscar Ortega-Recalde, ; Dora Janeth Fonseca-Mendoza,
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Angulo-Aguado M, Corredor-Orlandelli D, Carrillo-Martínez JC, Gonzalez-Cornejo M, Pineda-Mateus E, Rojas C, Triana-Fonseca P, Contreras Bravo NC, Morel A, Parra Abaunza K, Restrepo CM, Fonseca-Mendoza DJ, Ortega-Recalde O. Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population. Front Med (Lausanne) 2022; 9:910098. [PMID: 35795626 PMCID: PMC9251207 DOI: 10.3389/fmed.2022.910098] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/26/2022] [Indexed: 01/08/2023] Open
Abstract
Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2-26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79-0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.
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Affiliation(s)
- Mariana Angulo-Aguado
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - David Corredor-Orlandelli
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Juan Camilo Carrillo-Martínez
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Mónica Gonzalez-Cornejo
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Eliana Pineda-Mateus
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Carolina Rojas
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Paula Triana-Fonseca
- Department of Molecular Diagnosis, Genética Molecular de Colombia SAS, Bogotá, Colombia
| | - Nora Constanza Contreras Bravo
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Adrien Morel
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | | | - Carlos M. Restrepo
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Dora Janeth Fonseca-Mendoza
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
| | - Oscar Ortega-Recalde
- Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia
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Smith DH, Grewal J, Mehboob S, Mohan S, Pombo LF, Rodriguez P, Gonzalez JC, Zevallos J, Barengo NC. Association between ethnicity and hypertension in Northern Colombia in 2015. Clin Hypertens 2022; 28:18. [PMID: 35701852 PMCID: PMC9199244 DOI: 10.1186/s40885-022-00203-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 03/03/2022] [Indexed: 12/03/2022] Open
Abstract
Background Studies in the United States have shown a genetic predisposition to hypertension in individuals of African descent. However, studies on the associations between ethnic groups and hypertension in Latin America are lacking and the limited results have been inconsistent. The objective of this study is to determine whether Afro-Colombian ethnicity increases the risk of hypertension. Methods This study is a secondary data analysis of a cross sectional study from five provinces in Northern Colombia. Randomly selected individuals (N = 2613; age-range 18–74 years) enrolled in a health care insurance company underwent physical examinations and completed questionnaires regarding ethnicity, lifestyle, and other risk factors. Hypertension in these patients was determined. Unadjusted and adjusted logistic regression analysis were calculated to determine the association between ethnicity and hypertension. Results No association between Afro-Colombian ethnicity and hypertension was found (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.66–1.09). As expected, people with a body mass index (BMI) of 30 or higher were at a greater risk of having hypertension (OR, 3.12; 95% CI, 2.35–4.16) compared with those with a normal BMI. Conclusions Findings from this study suggest no independent association between Afro-Colombian ethnicity and hypertension. Further research should focus on genotyping or socioeconomic factors such as income level.
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Affiliation(s)
- Drew H Smith
- Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. .,Florida International University Herbert Wertheim College of Medicine, 11200 SW 8th Street, 33199, Miami, FL, USA.
| | - Jaskaran Grewal
- American University of Antigua, Osbourn, Antigua and Barbuda
| | - Saba Mehboob
- American University of Antigua, Osbourn, Antigua and Barbuda
| | - Shiva Mohan
- American University of Antigua, Osbourn, Antigua and Barbuda
| | - Luisa F Pombo
- Observatorio de Diabetes de Colombia, Organización para la Excelencia de la Salud, Bogotá, Colombia
| | - Pura Rodriguez
- Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Juan Carlos Gonzalez
- Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Juan Zevallos
- Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Noël C Barengo
- Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.,Department of Health Policy and Management, Robert Stempel College of Public Health and Social Work, Miami, FL, USA.,Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Mancera-Soto EM, Ramos-Caballero DM, Rojas J. JA, Duque L, Chaves-Gomez S, Cristancho-Mejía E, Schmidt WFJ. Hemoglobin Mass, Blood Volume and VO2max of Trained and Untrained Children and Adolescents Living at Different Altitudes. Front Physiol 2022; 13:892247. [PMID: 35721534 PMCID: PMC9204197 DOI: 10.3389/fphys.2022.892247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/18/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction: To a considerable extent, the magnitude of blood volume (BV) and hemoglobin mass (Hbmass) contribute to the maximum O2-uptake (VO2max), especially in endurance-trained athletes. However, the development of Hbmass and BV and their relationships with VO2max during childhood are unknown. The aim of the present cross-sectional study was to investigate Hbmass and BV and their relationships with VO2max in children and adolescents. In addition, the possible influence of endurance training and chronic hypoxia was evaluated.Methods: A total of 475 differently trained children and adolescents (girls n = 217, boys n = 258; untrained n = 171, endurance trained n = 304) living at two different altitudes (∼1,000 m, n = 204, ∼2,600 m, n = 271) and 9–18 years old participated in the study. The stage of puberty was determined according to Tanner; Hbmass and BV were determined by CO rebreathing; and VO2max was determined by cycle ergometry and for runners on the treadmill.Results: Before puberty, there was no association between training status and Hbmass or BV. During and after puberty, we found 7–10% higher values in the trained groups. Living at a moderate altitude had a uniformly positive effect of ∼7% on Hbmass in all groups and no effect on BV. The VO2max before, during and after puberty was strongly associated with training (pre/early puberty: boys +27%, girls +26%; mid puberty: +42% and +45%; late puberty: +43% and +47%) but not with altitude. The associated effects of training in the pre/early pubertal groups were independent of Hbmass and BV, while in the mid- and late pubertal groups, 25% of the training effect could be attributed to the elevated Hbmass.Conclusions: The associated effects of training on Hbmass and BV, resulting in increased VO2max, can only be observed after the onset of puberty.
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Affiliation(s)
- Erica Mabel Mancera-Soto
- Departamento del Movimiento Corporal Humano, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia
- Department of Sports Medicine and Sports Physiology, University of Bayreuth, Bayreuth, Germany
| | - Diana Marcela Ramos-Caballero
- Departamento de Biología, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia
- Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Joel A. Rojas J.
- Programa de Licenciatura en Educación Física Recreación y Deporte, Facultad de Ciencias de la Educación, Unidad Central del Valle del Cauca, Tuluá, Colombia
| | - Lohover Duque
- Programa de Licenciatura en Educación Física Recreación y Deporte, Facultad de Ciencias de la Educación, Unidad Central del Valle del Cauca, Tuluá, Colombia
| | - Sandra Chaves-Gomez
- Laboratorio de Control al Dopaje, Ministerio del Deporte de Colombia, Bogotá, Colombia
| | - Edgar Cristancho-Mejía
- Departamento de Biología, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Walter Franz-Joachim Schmidt
- Department of Sports Medicine and Sports Physiology, University of Bayreuth, Bayreuth, Germany
- *Correspondence: Walter Franz-Joachim Schmidt,
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Alarcón-Granados MC, Moreno-Ortíz H, Esteban-Pérez CI, Ferrebuz-Cardozo A, Camargo-Villalba GE, Forero-Castro M. Assessment of THADA gene polymorphisms in a sample of Colombian women with polycystic ovary syndrome: A pilot study. Heliyon 2022; 8:e09673. [PMID: 35711992 PMCID: PMC9194581 DOI: 10.1016/j.heliyon.2022.e09673] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 10/20/2021] [Accepted: 05/31/2022] [Indexed: 01/04/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a multifactorial and polygenic endocrine-metabolic disorder in women of reproductive age. SNPs in the THADA gene have been identified as PCOS risk loci. In this study, we evaluated the frequency of five polymorphisms in a sample of Colombian women with PCOS, and their association with clinical and endocrine-metabolic parameters. Forty-nine women with PCOS and forty-nine healthy women were included. Allelic discrimination was performed in the THADA gene by iPLEX and the MassARRAY system (Agena Bioscience). Haploview software was conducted to analyze the linkage disequilibrium (LD) and haplotypes of polymorphisms. There was an association between the genotypes TT of rs12468394, CC + AA of rs12468394, and GG of rs6544661 and an increase in the levels of free testosterone. The CC + AA of rs12468394 genotype also was associated with an increase of androstenedione levels. THADA gene SNPs were not associated with PCOS risk. There was very strong LD among the SNPs. No significant differences in the frequency of haplotypes between groups were observed. The statistical power of this analysis is low because of the small number of samples analyzed. Additional studies involving large populations of Colombian women with PCOS are needed to verify the role of the THADA gene in this disorder.
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Affiliation(s)
- Maria Camila Alarcón-Granados
- Facultad de Ciencias. Grupo de Investigación en Ciencias Biomédicas (GICBUPTC). Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia
| | | | | | - Atilio Ferrebuz-Cardozo
- Programa de Medicina. Facultad de Ciencias de La Salud. Universidad de Boyacá, Tunja, Colombia
| | | | - Maribel Forero-Castro
- Facultad de Ciencias. Grupo de Investigación en Ciencias Biomédicas (GICBUPTC). Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia
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Acosta-Uribe J, Aguillón D, Cochran JN, Giraldo M, Madrigal L, Killingsworth BW, Singhal R, Labib S, Alzate D, Velilla L, Moreno S, García GP, Saldarriaga A, Piedrahita F, Hincapié L, López HE, Perumal N, Morelo L, Vallejo D, Solano JM, Reiman EM, Surace EI, Itzcovich T, Allegri R, Sánchez-Valle R, Villegas-Lanau A, White CL, Matallana D, Myers RM, Browning SR, Lopera F, Kosik KS. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects. Genome Med 2022; 14:27. [PMID: 35260199 PMCID: PMC8902761 DOI: 10.1186/s13073-022-01035-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 02/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. METHODS We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. RESULTS We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. CONCLUSIONS Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.
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Affiliation(s)
- Juliana Acosta-Uribe
- Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - David Aguillón
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | | | - Margarita Giraldo
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
- Instituto Neurológico de Colombia (INDEC), Medellín, Colombia
| | - Lucía Madrigal
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Bradley W Killingsworth
- Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA
| | - Rijul Singhal
- Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA
| | - Sarah Labib
- Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA
| | - Diana Alzate
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Lina Velilla
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Sonia Moreno
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Gloria P García
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Amanda Saldarriaga
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Francisco Piedrahita
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Liliana Hincapié
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Hugo E López
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Nithesh Perumal
- Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA
| | - Leonilde Morelo
- Department of Internal Medicine, School of Medicine, Universidad del Sinú, Montería, Colombia
| | - Dionis Vallejo
- Department of Neurology, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Juan Marcos Solano
- Department of Neurology, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | | | - Ezequiel I Surace
- Laboratorio de Enfermedades Neurodegenerativas (Fleni-CONICET), Buenos Aires, Argentina
| | - Tatiana Itzcovich
- Laboratorio de Enfermedades Neurodegenerativas (Fleni-CONICET), Buenos Aires, Argentina
| | - Ricardo Allegri
- Centro de Memoria y Envejecimiento (Fleni-CONICET), Buenos Aires, Argentina
| | - Raquel Sánchez-Valle
- Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, IDIBAPS and University of Barcelona, Barcelona, Spain
| | - Andrés Villegas-Lanau
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia
| | - Charles L White
- Neuropathology Section, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Diana Matallana
- Instituto de Envejecimiento, Department of Psychiatry, School of Medicine, Pontifical Xaverian University, Bogotá, Colombia
- Department of Mental Health, Hospital Universitario Santa Fe de Bogotá, Bogotá, Colombia
| | - Richard M Myers
- HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
| | - Sharon R Browning
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Francisco Lopera
- Grupo de Neurociencias de Antioquia, School of Medicine, Universidad de Antioquia, Medellín, Colombia.
| | - Kenneth S Kosik
- Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA.
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Herrera M, Keynan Y, López L, Marín D, Arroyave L, Arbeláez MP, Vélez L, Rueda ZV. Incidence and Risk Factors Associated with Latent Tuberculosis Infection and Pulmonary Tuberculosis among People Deprived of Liberty in Colombian Prisons. Am J Trop Med Hyg 2022; 106:66-74. [PMID: 34872056 PMCID: PMC8733511 DOI: 10.4269/ajtmh.20-0307] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 08/30/2021] [Indexed: 01/03/2023] Open
Abstract
People deprived of liberty (PDL) are at high risk of acquiring Mycobacterium tuberculosis infection (latent tuberculosis infection [LTBI]) and progressing to active tuberculosis (TB). We sought to determine the incidence rates and factors associated with LTBI and active TB in Colombian prisons. Using information of four cohort studies, we included 240 PDL with two-step tuberculin skin test (TST) negative and followed them to evaluate TST conversion, as well as, 2,134 PDL that were investigated to rule out active TB (1,305 among people with lower respiratory symptoms of any duration, and 829 among people without respiratory symptoms and screened for LTBI). Latent tuberculosis infection incidence rate was 2,402.88 cases per 100,000 person-months (95% CI 1,364.62-4,231.10) in PDL with short incarceration at baseline, and 419.66 cases per 100,000 person-months (95% CI 225.80-779.95) in individuals with long incarceration at baseline (who were enrolled for the follow after at least 1 year of incarceration). The TB incidence rate among PDL with lower respiratory symptoms was 146.53 cases/100,000 person-months, and among PDL without respiratory symptoms screened for LTBI the incidence rate was 19.49 cases/100,000 person-months. History of Bacillus Calmette-Guerin vaccination decreased the risk of acquiring LTBI among PDL who were recently incarcerated. Female sex, smoked drugs, and current cigarette smoking were associated with an increased risk of developing active TB. This study shows that PDL have high risk for LTBI and active TB. It is important to perform LTBI testing at admission to prison, as well as regular follow-up to control TB in prisons.
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Affiliation(s)
| | - Yoav Keynan
- Department of Medical Microbiology and Infectious Diseases, Rady Faculty of Health Sciences University of Manitoba, Winnipeg, Manitoba, Canada
| | - Lucelly López
- Universidad Pontificia Bolivariana, Medellín, Colombia
| | - Diana Marín
- Universidad Pontificia Bolivariana, Medellín, Colombia
| | | | | | - Lázaro Vélez
- Universidad de Antioquia, Medellín, Antioquia, Colombia
| | - Zulma Vanessa Rueda
- Department of Medical Microbiology and Infectious Diseases, Rady Faculty of Health Sciences University of Manitoba, Winnipeg, Manitoba, Canada;,Universidad Pontificia Bolivariana, Medellín, Colombia;,Address correspondence to Zulma Vanessa Rueda, Department of Medical Microbiology and Infectious Diseases, Rady Faculty of Health Sciences, University of Manitoba, Rm 512, Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9. E-mail:
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Dary Gutiérrez-Castañeda L, Nova J, Irene Cerezo-Cortés M. Somatic Mutations in TP53 Gene in Colombian Patients With Non-melanoma Skin Cancer. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:107-114. [PMID: 35400008 PMCID: PMC8962838 DOI: 10.21873/cdp.10084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/03/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND/AIM Non-melanoma skin cancer is the most common cancer in the world. Somatic mutations in the TP53 gene are associated with the development of this cancer. To describe mutations in exons 5-8 of the TP53 gene in a sample of Colombian patients with non-melanoma skin cancer. MATERIALS AND METHODS One hundred and fifteen patients with non-melanoma skin cancer were included. Exons 5-8 were amplified and analyzed by PCR-High Resolution Melting and Sanger sequencing. RESULTS Fifty-seven patients with basal cell carcinomas and 58 with squamous cell carcinomas were studied. 16% of patients with basal cell carcinoma and 26% of patients with squamous cell carcinoma had mutations in the TP53 gene. The most frequent mutations were substitutions, while three patients had deletions. The most frequent mutation was p.R158G. CONCLUSION The analysis showed that Colombian individuals with non-melanoma skin cancer have genetic TP53 variants different from those reported as recurrent for this disease.
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Affiliation(s)
- Luz Dary Gutiérrez-Castañeda
- General Dermatology Group, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá, Colombia
| | - John Nova
- General Dermatology Group, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá, Colombia
| | - María Irene Cerezo-Cortés
- General Dermatology Group, Hospital Universitario Centro Dermatológico Federico Lleras Acosta E.S.E, Bogotá, Colombia
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Simão F, Ribeiro J, Vullo C, Catelli L, Gomes V, Xavier C, Huber G, Bodner M, Quiroz A, Ferreira AP, Carvalho EF, Parson W, Gusmão L. The Ancestry of Eastern Paraguay: A Typical South American Profile with a Unique Pattern of Admixture. Genes (Basel) 2021; 12:1788. [PMID: 34828394 PMCID: PMC8625094 DOI: 10.3390/genes12111788] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/25/2021] [Accepted: 11/09/2021] [Indexed: 11/17/2022] Open
Abstract
Immigrants from diverse origins have arrived in Paraguay and produced important demographic changes in a territory initially inhabited by indigenous Guarani. Few studies have been performed to estimate the proportion of Native ancestry that is still preserved in Paraguay and the role of females and males in admixture processes. Therefore, 548 individuals from eastern Paraguay were genotyped for three marker sets: mtDNA, Y-SNPs and autosomal AIM-InDels. A genetic homogeneity was found between departments for each set of markers, supported by the demographic data collected, which showed that only 43% of the individuals have the same birthplace as their parents. The results show a sex-biased intermarriage, with higher maternal than paternal Native American ancestry. Within the native mtDNA lineages in Paraguay (87.2% of the total), most haplogroups have a broad distribution across the subcontinent, and only few are concentrated around the Paraná River basin. The frequency distribution of the European paternal lineages in Paraguay (92.2% of the total) showed a major contribution from the Iberian region. In addition to the remaining legacy of the colonial period, the joint analysis of the different types of markers included in this study revealed the impact of post-war migrations on the current genetic background of Paraguay.
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Affiliation(s)
- Filipa Simão
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil; (F.S.); (J.R.); (A.P.F.); (E.F.C.)
| | - Julyana Ribeiro
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil; (F.S.); (J.R.); (A.P.F.); (E.F.C.)
| | - Carlos Vullo
- DNA Forensic Laboratory, Argentinean Forensic Anthropology Team, Córdoba 14001, Argentina; (C.V.); (L.C.)
| | - Laura Catelli
- DNA Forensic Laboratory, Argentinean Forensic Anthropology Team, Córdoba 14001, Argentina; (C.V.); (L.C.)
| | - Verónica Gomes
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4099-002 Porto, Portugal;
- Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), 4099-002 Porto, Portugal
| | - Catarina Xavier
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.X.); (G.H.); (M.B.)
| | - Gabriela Huber
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.X.); (G.H.); (M.B.)
| | - Martin Bodner
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.X.); (G.H.); (M.B.)
| | - Alfredo Quiroz
- Instituto de Previsión Social, Asunción 100153, Paraguay;
| | - Ana Paula Ferreira
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil; (F.S.); (J.R.); (A.P.F.); (E.F.C.)
| | - Elizeu F. Carvalho
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil; (F.S.); (J.R.); (A.P.F.); (E.F.C.)
| | - Walther Parson
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.X.); (G.H.); (M.B.)
- Forensic Science Program, The Pennsylvania State University, State College, PA 16801, USA
| | - Leonor Gusmão
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil; (F.S.); (J.R.); (A.P.F.); (E.F.C.)
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Niño-Sandoval TC, Vasconcelos BC. Biotypic classification of facial profiles using discrete cosine transforms on lateral radiographs. Arch Oral Biol 2021; 131:105249. [PMID: 34543809 DOI: 10.1016/j.archoralbio.2021.105249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 08/20/2021] [Accepted: 08/23/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE The aim of the study was to use discrete cosine transforms to graph soft tissue curves in lateral cephalometric radiographs and, with the obtained mathematical values, to group these curves by both traditional biotypes and cluster systems, in order to evaluate discriminatory capacity in terms of accuracy. DESIGN A sample of 625 lateral radiographs of adult patients (319 women and 306 men) was classified by facial biotype based on the ANB angle and mandibular plane angle. The curves of the facial profile were digitized with 50 equidistant points and discrete cosine transform was applied to analyze these curves mathematically for the determination of the accuracy of the classification of traditional biotypes. Phylogram cluster analysis was then performed for hierarchical grouping and accuracy was determined through cross-validation. RESULTS Grouping by biotype was performed for men and women separately. Although significant, accuracy did not surpass 71.4%. In the groups by clusters, significant results were achieved when performing four analyses for men and two for women. The best accuracy regarding classification power and qualitative distinction was 89.5% for men and 94% for women. CONCLUSIONS Discrete cosine transforms using a cluster system had greater discriminatory capacity in terms of accuracy compared to traditional grouping considering the ANB angle and mandibular plane angle. This exploration can be useful for the creation of a soft-tissue facial reconstruction software for the Latin American population.
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Affiliation(s)
- Tania Camila Niño-Sandoval
- University of Pernambuco - Santo Amaro Campus, Biological Sciences Institute, Specialization Course in Forensic Expertise, Recife, PE 50100-130, Brazil; University of Pernambuco, Pernambuco Dental School, Oswaldo Cruz University Hospital, Department of Oral and Maxillofacial Surgery and Traumatology, Recife, PE 50100-130, Brazil
| | - Belmiro C Vasconcelos
- University of Pernambuco, Pernambuco Dental School, Oswaldo Cruz University Hospital, Department of Oral and Maxillofacial Surgery and Traumatology, Recife, PE 50100-130, Brazil.
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Olaya-Galán NN, Salas-Cárdenas SP, Rodriguez-Sarmiento JL, Ibáñez-Pinilla M, Monroy R, Corredor-Figueroa AP, Rubiano W, de la Peña J, Shen H, Buehring GC, Patarroyo MA, Gutierrez MF. Risk factor for breast cancer development under exposure to bovine leukemia virus in Colombian women: A case-control study. PLoS One 2021; 16:e0257492. [PMID: 34547016 PMCID: PMC8454960 DOI: 10.1371/journal.pone.0257492] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 09/02/2021] [Indexed: 11/19/2022] Open
Abstract
Viruses have been implicated in cancer development in both humans and animals. The role of viruses in cancer is typically to initiate cellular transformation through cellular DNA damage, although specific mechanisms remain unknown. Silent and long-term viral infections need to be present, in order to initiate cancer disease. In efforts to establish a causative role of viruses, first is needed to demonstrate the strength and consistency of associations in different populations. The aim of this study was to determine the association of bovine leukemia virus (BLV), a causative agent of leukemia in cattle, with breast cancer and its biomarkers used as prognosis of the severity of the disease (Ki67, HER2, hormonal receptors) in Colombian women. An unmatched, observational case-control study was conducted among women undergoing breast surgery between 2016-2018. Malignant samples (n = 75) were considered as cases and benign samples (n = 83) as controls. Nested-liquid PCR, in-situ PCR and immunohistochemistry were used for viral detection in blood and breast tissues. For the risk assessment, only BLV positive samples from breast tissues were included in the analysis. BLV was higher in cases group (61.3%) compared with controls (48.2%), with a statistically significant association between the virus and breast cancer in the unconditional logistic regression (adjusted-OR = 2.450,95%CI:1.088-5.517, p = 0.031). In this study, BLV was found in both blood and breast tissues of participants and an association between breast cancer and the virus was confirmed in Colombia, as an intermediate risk factor.
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Affiliation(s)
- Nury N. Olaya-Galán
- PhD Program in Biomedical and Biological Sciences, Universidad del Rosario, Bogotá, Colombia
- Grupo de Enfermedades Infecciosas, Laboratorio de Virología, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Sandra P. Salas-Cárdenas
- Grupo de Enfermedades Infecciosas, Laboratorio de Virología, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Jorge L. Rodriguez-Sarmiento
- Department of Pathology, Hospital Universitario San Ignacio - Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Ricardo Monroy
- Hospital Universitario Mayor Méderi – Universidad del Rosario, Bogotá, Colombia
| | - Adriana P. Corredor-Figueroa
- Grupo de Enfermedades Infecciosas, Laboratorio de Virología, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Wilson Rubiano
- Hospital Universitario Mayor Méderi – Universidad del Rosario, Bogotá, Colombia
| | - Jairo de la Peña
- Hospital Universitario Mayor Méderi – Universidad del Rosario, Bogotá, Colombia
| | - HuaMin Shen
- School of Public Health, University of California, Berkeley, California, United States of America
| | - Gertrude C. Buehring
- School of Public Health, University of California, Berkeley, California, United States of America
| | - Manuel A. Patarroyo
- Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia
- Microbiology Department, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia
- Health Sciences Division, Main Campus, Universidad Santo Tomás, Bogotá, Colombia
| | - Maria F. Gutierrez
- Grupo de Enfermedades Infecciosas, Laboratorio de Virología, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, Colombia
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Romero-Sánchez C, Hernández N, Chila-Moreno L, Jiménez K, Padilla D, Bello-Gualtero JM, Bautista-Molano W. HLA-B Allele, Genotype, and Haplotype Frequencies in a Group of Healthy Individuals in Colombia. J Clin Rheumatol 2021; 27:S148-S152. [PMID: 33790206 DOI: 10.1097/rhu.0000000000001671] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The sequencing of alleles of the HLA-B, a human leukocyte antigen (HLA) class I gene, was established as the most polymorphic of chromosome 6 and of the entire human genome. In this locus, the HLA-B*27 allele is highly polymorphic and has clinical relevance. Literature about the subtypes and singular frequency of these alleles in Colombia's healthy population is scarce. OBJECTIVE The aim of this study was to establish the HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population and analyze their association with the sex and geographical distribution of the individuals studied. METHODS This is a nonexperimental and descriptive study. The data from whole-blood samples whose HLA genes were genotyped by protocol with the Luminex 100/200 xMAP technology were evaluated. HLA-B*27 positivity was confirmed by the new-generation sequencing technology. The associations between the HLA-B alleles and demographic variables were evaluated by χ2 and Fisher exact tests. RESULTS Twenty-seven HLA-B genotypes were identified in 255 individuals, with the highest frequencies for HLA-B*35 (44.7%), B*40 (19.6%), and B*44 (16.8%). Additionally, 89 HLA-B alleles were found; the most common were HLA-B*35:01 (6.7%) and B*40:02 (6.5%). Nine individuals tested positive for the HLA-B*27 allele with genotype and allele frequencies of 3.5% and 1.8%, respectively; the HLA-B*27:05:02 subtype predominated. CONCLUSIONS Here, we report the most common HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population group and analyzed their association with the sex and geographical distribution of the individuals studied. Results for the HLA-B*27 allele confirm racial mixing in Colombia with a high degree of Caucasian influence, as well as the repopulation of Colombia's central region, attributed to the migration phenomena. Results agree with data published in Colombia that was obtained from cord blood samples.
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Affiliation(s)
| | - Natalia Hernández
- Bacteriology Program, Faculty of Basic Sciences, Universidad Colegio Mayor de Cundinamarca, Bogotá
| | - Lorena Chila-Moreno
- Clinical Immunology Group, Hospital Militar Central, School of Medicine, Universidad Militar Nueva Granada
| | - Karen Jiménez
- Pediatric Rheumatology Program, Faculty of Medicine, Universidad El Bosque
| | - Diana Padilla
- Rheumatology Program, Faculty of Medicine Universidad de la Sabana, Universidad de La Sabana, Chia, Colombia
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López-Cáceres A, Velasco-Rueda M, Garcia-Cifuentes E, Zarante I, Matallana D. Analysis of Heritability Across the Clinical Phenotypes of Frontotemporal Dementia and the Frequency of the C9ORF72 in a Colombian Population. Front Neurol 2021; 12:681595. [PMID: 34526954 PMCID: PMC8435669 DOI: 10.3389/fneur.2021.681595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 06/30/2021] [Indexed: 12/04/2022] Open
Abstract
Frontotemporal dementia (FTD) is a highly heritable condition. Up to 40% of FTD is familial and an estimated 15% to 40% is due to single-gene mutations. It has been estimated that the G4C2 hexanucleotide repeat expansions in the C9ORF72 gene can explain up to 37.5% of the familial cases of FTD, especially in populations of Caucasian origin. The purpose of this paper is to evaluate hereditary risk across the clinical phenotypes of FTD and the frequency of the G4C2 expansion in a Colombian cohort diagnosed with FTD. Methods: A total of 132 FTD patients were diagnosed according to established criteria in the behavioral variant FTD, logopenic variant PPA, non-fluent agrammatic PPA, and semantic variant PPA. Hereditary risk across the clinical phenotypes was established in four categories that indicate the pathogenic relationship of the mutation: high, medium, low, and apparently sporadic, based on those proposed by Wood and collaborators. All subjects were also examined for C9ORF72 hexanucleotide expansion (defined as >30 repetitions). Results: There were no significant differences in the demographic characteristics of the patients between the clinical phenotypes of FTD. The higher rate phenotype was bvFTD (62.12%). In accordance with the risk classification, we found that 72 (54.4%) complied with the criteria for the sporadic cases; for the familial cases, 23 (17.4%) fulfilled the high-risk criteria, 23 (17.4%) fulfilled the low risk criteria, and 14 (10.6%) fulfilled the criteria to be classified as subject to medium risk. C9ORF72 expansion frequency was 0.76% (1/132). Conclusion: The FTD heritability presented in this research was very similar to the results reported in the literature. The C9ORF72 expansion frequency was low. Colombia is a triethnic country, with a high frequency of genetic Amerindian markers; this shows consistency with the present results of a low repetition frequency. This study provides an initial report of the frequency for the hexanucleotide repeat expansions in C9ORF72 in patients with FTD in a Colombian population and paves the way for further study of the possible genetic causes of FTD in Colombia.
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Affiliation(s)
- Andrea López-Cáceres
- School of Medicine, Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia
- Fundación Santa Fé de Bogotá, Bogotá, Colombia
| | - María Velasco-Rueda
- School of Medicine, Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Elkin Garcia-Cifuentes
- School of Medicine, Departamento de Neurociencias, Unidad de neurología, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Ignacio Zarante
- School of Medicine, Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Diana Matallana
- Fundación Santa Fé de Bogotá, Bogotá, Colombia
- School of Medicine, Instituto de Envejecimiento, Doctorado de Neurociencias, Psychiatry and Mental Health Department, Pontificia Universidad Javeriana, Bogotá, Colombia
- Centro de Memoria y Cognición Intellectus, Hospital Universitario San Ignacio, Bogotá, Colombia
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Flores-Espinoza R, Paz-Cruz E, Ruiz-Pozo VA, Lopez-Carrera M, Cabrera-Andrade A, Gusmão L, Burgos G. Investigating genetic diversity in admixed populations from Ecuador. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2021; 176:109-119. [PMID: 34169504 DOI: 10.1002/ajpa.24341] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/21/2021] [Accepted: 05/23/2021] [Indexed: 11/10/2022]
Abstract
OBJECTIVES According to demographic history, Ecuador has experienced shifts in its Native American populations caused by European colonization and the African slave trade. The continuous admixture events among Europeans, Native Americans, and Africans occurred differently in each region of the country, producing a stratified population. Thus, the aim of this study was to investigate the level of genetic substructure in the Ecuadorian Mestizo population. MATERIALS AND METHODS A total of 377 male and 209 female samples were genotyped for two sets of X-chromosomal markers (32 X-Indels and 12 X-STRs). Population analyses performed included Hardy-Weinberg equilibrium tests, LD analysis, PCA, pairwise FST s, and AMOVA. RESULTS Significant levels of LD were observed between markers separated by distances of less than 1 cM, as well as between markers separated by distances varying from 10.891 to 163.53 cM. Among Ecuadorian regions, Amazonia showed the highest average R2 value. DISCUSSION When X-chromosomal and autosomal differentiation values were compared, a sex-biased admixture between European men and Native American and African women was revealed, as well as between African men and Native American women. Moreover, a distinct Native American ancestry was discernible in the Amazonian population, in addition to sex-biased gene flow between Amazonia and the Andes and Pacific coast regions. Overall, these results underline the importance of integrating X chromosome information to achieve a more comprehensive view of the genetic and demographic histories of South American admixed populations.
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Affiliation(s)
- Rodrigo Flores-Espinoza
- Laboratório de Diagnóstico por DNA (LDD), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.,Laboratorios de Investigación, Universidad de Las Américas (UDLA), Quito, Ecuador
| | - Elius Paz-Cruz
- Laboratorio de ADN, Fiscalía General del Estado, Quito, Ecuador
| | | | | | - Alejandro Cabrera-Andrade
- Grupo de Bio-Quimioinformática, Universidad de Las Américas (UDLA), Quito, Ecuador.,Carrera de Enfermería, Facultad de Ciencias de la Salud, Universidad de Las Américas (UDLA), Quito, Ecuador
| | - Leonor Gusmão
- Laboratório de Diagnóstico por DNA (LDD), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - German Burgos
- Escuela de Medicina, Facultad de Ciencias de la Salud, Universidad de Las Américas (UDLA), Quito, Ecuador.,Grupo de Medicina Xenómica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
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Patterns of genetic diversity in Colombia for 38 indels used in human identification. Forensic Sci Int Genet 2021; 53:102495. [PMID: 33743518 DOI: 10.1016/j.fsigen.2021.102495] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/06/2021] [Indexed: 01/15/2023]
Abstract
The current population of Colombia has a genetic heterogeneity resulting from different migrations from other continents and within the country. In addition, there are small groups in their territory that have remained isolated and therefore have a different genetic pool in relation to that of the neighbouring urban populations. This population stratification must be considered in forensic analysis, being more complex for markers with marked intercontinental differentiation. In this study, population differentiation in Colombian admixed, native, and Afro-descendant populations was evaluated for a group of 38 indels described for forensic use. Allelic frequencies and parameters of forensic relevance were determined in each of the groups defined based on population differentiation analyses. In addition to the differences found between population groups, the results show that the set of 38 indels analysed could be useful in studies of individual identification in Colombia. The exclusion power presented by this set of markers suggests the need for joint use with other markers, being able to complement the STRs in paternity cases. High levels of both power of discrimination and exclusion were found when complementing the 38 HID-indels with a second multiplex, for a total of 83 indels.
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Mario-Vásquez JE, Naranjo-González CA, Montiel J, Zuluaga LM, Vásquez AM, Tobón-Castaño A, Bedoya G, Segura C. Association of variants in IL1B, TLR9, TREM1, IL10RA, and CD3G and Native American ancestry on malaria susceptibility in Colombian populations. INFECTION GENETICS AND EVOLUTION 2020; 87:104675. [PMID: 33316430 DOI: 10.1016/j.meegid.2020.104675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 11/19/2020] [Accepted: 12/09/2020] [Indexed: 12/24/2022]
Abstract
Host genetics is an influencing factor in the manifestation of infectious diseases. In this study, the association of mild malaria with 28 variants in 16 genes previously reported in other populations and/or close to ancestry-informative markers (AIMs) selected was evaluated in an admixed 736 Colombian population sample. Additionally, the effect of genetic ancestry on phenotype expression was explored. For this purpose, the ancestral genetic composition of Turbo and El Bagre was determined. A higher Native American ancestry trend was found in the population with lower malaria susceptibility [odds ratio (OR) = 0.416, 95% confidence interval (95% CI) = 0.234-0.740, P = 0.003]. Three AIMs presented significant associations with the disease phenotype (MID1752, MID921, and MID1586). The first two were associated with greater malaria susceptibility (D/D, OR = 2.23, 95% CI = 1.06-4.69, P = 0.032 and I/D-I/I, OR = 2.14, 95% CI = 1.18-3.87, P = 0.011, respectively), and the latter has a protective effect on the appearance of malaria (I/I, OR = 0.18, 95% CI = 0.08-0.40, P < 0.0001). After adjustment by age, sex, municipality, and genetic ancestry, genotype association analysis showed evidence of association with malaria susceptibility for variants in or near IL1B, TLR9, TREM1, IL10RA, and CD3G genes: rs1143629-IL1B (G/A-A/A, OR = 0.41, 95% CI = 0.21-0.78, P = 0.0051), rs352139-TLR9 (T/T, OR = 0.28, 95% CI = 0.11-0.72, P = 0.0053), rs352140-TLR9 (C/C, OR = 0.41, 95% CI = 0.20-0.87, P = 0.019), rs2234237-TREM1 (T/A-A/A, OR = 0.43, 95% CI = 0.23-0.79, P = 0.0056), rs4252246-IL10RA (C/A-A/A, OR = 2.11, 95% CI = 1.18-3.75, P = 0.01), and rs1561966-CD3G (A/A, OR = 0.20, 95% CI = 0.06-0.69, P = 0.0058). The results showed the participation of genes involved in immunological processes and suggested an effect of ancestral genetic composition over the traits analyzed. Compared to the paisa population (Antioquia), Turbo and El Bagre showed a strong decrease in European ancestry and an increase in African and Native American ancestries. Also, a novel association of two single nucleotide polymorphisms with malaria susceptibility was identified in this study.
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Affiliation(s)
- Jorge Eliécer Mario-Vásquez
- Grupo Genética Molecular (GENMOL), Universidad de Antioquia, Carrera 53 No. 61-30, Lab 430. Medellín, Colombia
| | | | - Jehidys Montiel
- Grupo Malaria-Facultad de Medicina, Universidad de Antioquia, Carrera 53 No. 61-30, Lab 610, Medellín, Colombia
| | - Lina M Zuluaga
- Grupo Malaria-Facultad de Medicina, Universidad de Antioquia, Carrera 53 No. 61-30, Lab 610, Medellín, Colombia
| | - Ana M Vásquez
- Grupo Malaria-Facultad de Medicina, Universidad de Antioquia, Carrera 53 No. 61-30, Lab 610, Medellín, Colombia
| | - Alberto Tobón-Castaño
- Grupo Malaria-Facultad de Medicina, Universidad de Antioquia, Carrera 53 No. 61-30, Lab 610, Medellín, Colombia
| | - Gabriel Bedoya
- Grupo Genética Molecular (GENMOL), Universidad de Antioquia, Carrera 53 No. 61-30, Lab 430. Medellín, Colombia
| | - Cesar Segura
- Grupo Malaria-Facultad de Medicina, Universidad de Antioquia, Carrera 53 No. 61-30, Lab 610, Medellín, Colombia.
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Seroprevalence of Antitransglutaminase and Antiendomysium Antibodies in Adult Colombian Blood Bank Donors. Can J Gastroenterol Hepatol 2020; 2020:7541941. [PMID: 33335872 PMCID: PMC7723479 DOI: 10.1155/2020/7541941] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 11/10/2020] [Accepted: 11/20/2020] [Indexed: 12/12/2022] Open
Abstract
Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten from wheat, barley, and rye in genetically susceptible individuals. The global prevalence of CD is 1.4%. However, most of the prevalence studies have been conducted in Caucasian populations; few studies have been performed in Latin America. The aim of this study is to determine the seroprevalence of auto-antibodies used as markers for CD in a Colombian cohort. In this cross-sectional study, the serum samples from Colombian donors of the National Red Cross Blood Bank were collected between June and September 2017 in Bogotá, Colombia. All sera were tested for IgA antitissue transglutaminase (TTG) by enzyme-linked immunosorbent assay. Seropositive sera were tested for IgA antiendomysium (EMA) using indirect immunofluorescence assay. The ancestral genetic composition was determined in donor samples with antibody assay reactivity. Those with two seroreactive assays were typed for HLA class II DQ2 and DQ8. In total, 228 blood donors participated in the study. Among them, 113 were females (49.56%) with an average age of 31.63 years (SD ± 12.99); males had an average of 34.71 years (SD ± 13.01). Only 3 (1.31%) donors reported chronic diarrhea and nonintentional weight loss; 11 (4.82%) had a family history of CD. For the serological assays, 11 donors (4.82%) were seroreactive to IgA anti-TTG: 3 had high reactivity and 8 had low reactivity. Of those seroreactive to IgA anti-TTG, 3 (1.32%) were also seroreactive to anti-EMA, and they were typed as HLA-DQ8 or HLA-DQ2. The baseline ancestral percentage of the seroreactive donors was higher for European and Native American than for African genes. The seroprevalence for anti-TTG and anti-EMA with the presence of HLA-DQ8 and HLA-DQ2 was 1.32%. Additionally, 4.82% donor participants were reactive only for anti-TTG. Compared with other studies, our findings suggest that Colombia has a high prevalence of CD markers.
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Mogollón Olivares F, Moncada Madero J, Casas-Vargas A, Zea Montoya S, Suárez Medellín D, Gusmão L, Usaquén W. Contrasting the ancestry patterns of three distinct population groups from the northernmost region of South America. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2020; 173:437-447. [PMID: 32856314 DOI: 10.1002/ajpa.24130] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 07/21/2020] [Accepted: 07/24/2020] [Indexed: 01/15/2023]
Abstract
Colombia, located in the north of the South American subcontinent is a country of great interest for population genetic studies given its high ethnic and cultural diversity represented by the admixed population, 102 indigenous peoples and African descent populations. In this study, an analysis of the genetic structure and ancestry was performed based on 46 ancestry informative INDEL markers (AIM-INDELs) and considering the genealogical and demographic variables of 451 unrelated individuals belonging to nine Native American, two African American, and four multiple ancestry populations. Measures of genetic diversity, ancestry components, and genetic substructure were analyzed to build a population model typical of the northernmost part of the South American continent. The model suggests three types of populations: Native American, African American, and multiple ancestry. The results support hypotheses posed by other authors about issues like the peopling of South America and the existence of two types of Native American ancestry. This last finding could be crucial for future research on the peopling of Colombia and South America in that a single origin of all indigenous communities should not be assumed. It then would be necessary to consider other events that could explain their genetic variability and complexity throughout the continent.
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Affiliation(s)
| | - Julie Moncada Madero
- Population Genetics and Identification Group, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Andrea Casas-Vargas
- Population Genetics and Identification Group, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Sara Zea Montoya
- Population Genetics and Identification Group, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Dayana Suárez Medellín
- Population Genetics and Identification Group, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Leonor Gusmão
- DNA Diagnostic Laboratory, Universidade do Estado de Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
| | - William Usaquén
- Population Genetics and Identification Group, Universidad Nacional de Colombia, Bogotá, Colombia
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Tovar-Parra JD, Gutiérrez-Castañeda LD, Gil-Quiñones SR, Nova JA, Pulido L. CDKN2A Polymorphism in Melanoma Patients in Colombian Population: A Case-Control Study. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7458917. [PMID: 33102592 PMCID: PMC7576359 DOI: 10.1155/2020/7458917] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/06/2020] [Accepted: 10/03/2020] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Melanoma is the most aggressive type of skin cancer, with poor prognosis in advanced stages. The incidence and mortality rates have increased in recent years. Single nucleotide polymorphisms p.R24P, p.M53I, p.G101W, p.V126D, and p.A148T in the CDKN2A (HGNC ID: 1787) gene have been associated with the development of melanoma in different populations; however, this association has not been studied in Colombia. METHODS Cutaneous melanoma patients and healthy controls (85 cases and 166 controls) were included in this study. These subjects were screened through HRM-qPCR assay and detected variants in exon 1 and 2 of CDKN2A gene and confirmed with Sanger sequencing. Chi-square test was used to compare allele and genotype distributions between cases and controls. Odds ratio (OR) with 95% confidence interval (CI) was calculated to determine the association between polymorphisms and haplotypes with melanoma susceptibility. Statistical and haplotype analyses were performed using Stata® and R-Studio®. RESULTS Fifty-four percent of women were identified both in cases and controls. The frequencies of melanoma subtypes were 36,47% lentigo maligna, 24,71% acral lentiginous, 23,53% superficial extension, and 15,29% nodular. Variants in the CDKN2A gene were 11.76% in cases and 8.43% in controls. The most frequent was p.A148T in 5.88% of cases and in 4.82% of controls. GGTTG haplotype showed statistically significant differences between cases and controls (p value = 0.04). CONCLUSION CDKN2A polymorphisms p.G101W, p.R24P, p.M53I, and A148T are not associated with melanoma susceptibility in the Colombian population; further studies regarding genetic interaction and additive effects between more variants are required.
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Affiliation(s)
- Jose D. Tovar-Parra
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta, E.S.E., DC, Bogotá, Colombia 111511, Colombia
| | - Luz D. Gutiérrez-Castañeda
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta, E.S.E., DC, Bogotá, Colombia 111511, Colombia
| | - Sebastián R. Gil-Quiñones
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta, E.S.E., DC, Bogotá, Colombia 111511, Colombia
| | - Jhon A. Nova
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta, E.S.E., DC, Bogotá, Colombia 111511, Colombia
| | - Leonardo Pulido
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta, E.S.E., DC, Bogotá, Colombia 111511, Colombia
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Gutiérrez-Castañeda LD, Gamboa M, Nova JA, Pulido L, Tovar-Parra JD. Mutations in the BRAF, NRAS, and C-KIT Genes of Patients Diagnosed with Melanoma in Colombia Population. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2046947. [PMID: 32775409 PMCID: PMC7396105 DOI: 10.1155/2020/2046947] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 06/05/2020] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Mutations in the BRAF, NRAS, and C-KIT genes have been associated with the histopathological characteristics of melanoma. Likewise, the incidence of each of these subtypes changes according to the geographical origin of the population analyzed. OBJECTIVE To determine the mutation frequency in exons 11 and 15 of the BRAF gene, exons 1 and 2 of the NRAS gene, and exons 11, 13, and 17 of the C-KIT gene and to relate it with histological subtypes in patients from a region with high levels of ultraviolet radiation. Methodology. The clinicopathological characteristics of 54 cutaneous melanoma samples were analyzed. Mutation analysis was performed via qPCR on paraffin-embedded tumor tissue samples using probes specific for the V600E mutation. Amplification of exons 11 and 15 of the BRAF gene, exons 1 and 2 of the NRAS gene, and exons 11, 13, and 17 of the C-KIT gene was performed for subsequent sequencing using the Sanger method. RESULT The most frequent histological subtype in the analyzed sample was lentigo maligna/lentigo maligna melanoma (52%) followed by acral lentiginous melanoma (20%). The BRAF-V600 variant was the most frequent (63.6%). The most frequent (54%) mutation in NRAS was p.Lys5∗. In the C-KIT gene, only the Val560Ala mutation was found. CONCLUSION Differences in histological subtypes and mutations in the BRAF, NRAS, and C-KIT genes were found in the analyzed population. This indicates that environmental and genetic factors significantly influence the introduction of the disease in this geographic region.
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Affiliation(s)
| | - Mauricio Gamboa
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta-CDFLLA, Bogota 111511, Colombia
| | - John A. Nova
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta-CDFLLA, Bogota 111511, Colombia
| | - Leonardo Pulido
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta-CDFLLA, Bogota 111511, Colombia
| | - Jose D. Tovar-Parra
- Hospital Universitario-Centro Dermatológico Federico Lleras Acosta-CDFLLA, Bogota 111511, Colombia
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