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Zamudio-Felix I, Barron-Cabrera E, Rangel-Villalobos H, Gonzalez-Becerra K. Predicted risk genotypes to cardiovascular diseases based on cholesterol ester transfer protein (CETP -rs708272) and lipoprotein lipase (LPL -rs13702) variants in worldwide populations: highest risk in populations with Native American ancestry. Mol Biol Rep 2025; 52:442. [PMID: 40310538 DOI: 10.1007/s11033-025-10537-9] [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: 01/18/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND The human genetic variability mainly involves single nucleotide variants (SNVs) that determine the characteristics among individuals. Some gene variants related to the lipid metabolism have demonstrated their importance to generate susceptibility to some metabolic diseases, such as those in the Cholesterol Ester Transfer Protein (CETP) and Lipoprotein Lipase (LPL) genes. METHODS AND RESULTS We analyzed the variants rs708272 and rs13702 of the CETP and LPL genes in 540 Mexican Mestizos (admixed) and Mexican Native Americans, respectively. The SNVs were analyzed by qPCR with TaqMan probes. The GeneAlex 6.0, GDA 1.1, and Arlequin 3.0 softwares were used for statistical analysis. RESULTS Genotype and allele frequencies for these variants in the CETP and LPL genes were estimated. The Analysis of Molecular Variance (AMOVA) including Mexican and worldwide populations from the 1000 genomes project, demonstrated significant genetic heterogeneity for both variants (p-value < 0.0001). Based on previous association studies, we predicted the genetic risk to cardiovascular diseases in global populations using combined high-risk allele frequencies (TT + TT), whose prevalence was larger in Native Americans than Mestizos (21.6 vs 11.7%; p = 0. 044). Globally, Peru showed the largest prevalence (21%) and African populations the lowest (1%). CONCLUSION Based on the rs13702 and rs708272 gene variants, the highest predicted genetic risk levels for cardiovascular diseases is related to populations with high Native American ancestry, such as those from Latin America, especially when combined with obesogenic habits. Understanding genetic distribution of these variants in Mexican population could suggest an integral intervention for the management of cardiovascular diseases.
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Affiliation(s)
- Itzel Zamudio-Felix
- Department of Medical and Life Sciences, University Center of Cienega, Molecular Genetics Research Institute Ocotlan, University of Guadalajara, Jalisco, Mexico
| | | | - Héctor Rangel-Villalobos
- Department of Medical and Life Sciences, University Center of Cienega, Molecular Genetics Research Institute Ocotlan, University of Guadalajara, Jalisco, Mexico.
| | - Karina Gonzalez-Becerra
- Department of Medical and Life Sciences, University Center of Cienega, Molecular Genetics Research Institute Ocotlan, University of Guadalajara, Jalisco, Mexico.
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León-Reyes G, Argoty-Pantoja AD, Rivera-Paredez B, Hidalgo-Bravo A, Flores YN, Salmerón J, Velázquez-Cruz R. Interaction between SIDT2 and ABCA1 Variants with Nutrients on HDL-c Levels in Mexican Adults. Nutrients 2023; 15:370. [PMID: 36678241 PMCID: PMC9861312 DOI: 10.3390/nu15020370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/09/2022] [Accepted: 11/15/2022] [Indexed: 01/13/2023] Open
Abstract
Previous studies have reported that the SIDT2 and ABCA1 genes are involved in lipid metabolism. We aimed to analyze the association-the gene x gene interaction between rs17120425 and rs1784042 on SIDT2 and rs9282541 on ABCA1 and their diet interaction on the HDL-c serum levels-in a cohort of 1982 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. The associations and interactions of interest were estimated using linear and logistic regression. Carriers of the rs17120425-A and rs1784042-A alleles had slightly higher blood HDL-c levels compared to the non-carriers. In contrast, rs9282541-A was associated with low blood HDL-c levels (OR = 1.34, p = 0.013). The rs1784042 x rs9282541 interaction was associated with high blood HDL-c levels (p = 3.4 × 10-4). Premenopausal women who carried at least one rs17120425-A allele and consumed high dietary fat, protein, monounsaturated, or polyunsaturated fatty acids levels had higher HDL-c levels than the non-carriers. These results support the association between the genetic variants on SIDT2 and ABCA1 with HDL-c levels and suggest gene-gene and gene-diet interactions over HDL-c concentrations in Mexican adults. Our findings could be a platform for developing clinical and dietary strategies for improving the health of the Mexican population.
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Affiliation(s)
- Guadalupe León-Reyes
- Genomics of Bone Metabolism Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City 14610, Morelos, Mexico
| | - Anna D. Argoty-Pantoja
- Research Center in Policies, Population and Health, School of Medicine, National Autonomous University of Mexico (UNAM), Mexico City 04510, Morelos, Mexico
| | - Berenice Rivera-Paredez
- Research Center in Policies, Population and Health, School of Medicine, National Autonomous University of Mexico (UNAM), Mexico City 04510, Morelos, Mexico
| | - Alberto Hidalgo-Bravo
- Department of Genetics, National Institute of Rehabilitation (INR), Mexico City 014389, Morelos, Mexico
| | - Yvonne N. Flores
- Epidemiological and Health Services Research Unit, Morelos, Mexican Institute of Social Security, Cuernavaca 62000, Morelos, Mexico
- Department of Health Policy and Management and Kaiser Permanente Center for Health Equity, Fielding School of Public Health, Los Angeles, University of California, Los Angeles, CA 90095, USA
- Cancer Prevention and Control Research Center, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA
| | - Jorge Salmerón
- Research Center in Policies, Population and Health, School of Medicine, National Autonomous University of Mexico (UNAM), Mexico City 04510, Morelos, Mexico
| | - Rafael Velázquez-Cruz
- Genomics of Bone Metabolism Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City 14610, Morelos, Mexico
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Ajabnoor GMA, Bahijri SM, Alrashidi W, Enani SM, Alamoudi AA, Al Sheikh L, Eldakhakhny B. ABCA1 C69T Gene Polymorphism Association with Dysglycemia in Saudi Prediabetic Adults. Genes (Basel) 2022; 13:genes13122277. [PMID: 36553543 PMCID: PMC9777653 DOI: 10.3390/genes13122277] [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: 10/20/2022] [Revised: 11/21/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open
Abstract
Studies suggest that ATP-binding cassette transporter A1 (ABCA1 C69T) polymorphism is associated with a decreased incidence of type 2 diabetes mellitus (T2DM) and that there is an association between ABCA1 C69T polymorphism and the risk of dyslipidemia in diabetic individuals. However, other studies contradict these suggestions. Therefore, we aimed to investigate the prevalence of ABCA1 C69T (rs1800977) gene polymorphism in a representative sample of the Saudi population not previously diagnosed with diabetes and its possible association with dyslipidemia and dysglycemia. A cross-sectional design was used to recruit nondiabetic adults of both genders from the Saudi population in Jeddah by employing a stratified, two-stage cluster sampling method. A total of 650 people (337 men and 313 women) were recruited. Demographic, dietary, and lifestyle variables, as well as medical history and family history of chronic diseases, were collected using a predesigned questionnaire. Fasting blood samples were taken for the determination of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and lipids profile, which were followed by a 1-h oral glucose tolerance test (OGTT). Real-time PCR technology was used to determine the ABCA1 C69T gene SNP (rs1800977). The T allele of ABCA1 C69T (rs1800977) was very frequent (TT in 44.9% and CT in 43.7%). There was a trend toward significance for a higher dysglycemia percentage in people with CT and TT genotypes (25.7%, and 23.3%, respectively) compared with CC genotypes (16.2%). In addition, FPG and 1-h plasma glucose were significantly higher in people with both TT and CT genotypes compared to CC genotypes. However, T allele was not associated with any dysregulation of lipid parameters.
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Affiliation(s)
- Ghada M. A. Ajabnoor
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21551, Saudi Arabia
- Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 3270, Saudi Arabia
- Food, Nutrition and Lifestyle Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 3270, Saudi Arabia
- Correspondence:
| | - Suhad M. Bahijri
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21551, Saudi Arabia
- Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 3270, Saudi Arabia
- Food, Nutrition and Lifestyle Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 3270, Saudi Arabia
| | - Wafa Alrashidi
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21551, Saudi Arabia
| | - Sumia Mohammad Enani
- Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 3270, Saudi Arabia
- Food, Nutrition and Lifestyle Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 3270, Saudi Arabia
- Department of Food and Nutrition, Faculty of Human Sciences and Design, King Abdulaziz University, Jeddah 3270, Saudi Arabia
| | - Aliaa A. Alamoudi
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21551, Saudi Arabia
- Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 3270, Saudi Arabia
| | - Lubna Al Sheikh
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Basmah Eldakhakhny
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21551, Saudi Arabia
- Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 3270, Saudi Arabia
- Food, Nutrition and Lifestyle Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 3270, Saudi Arabia
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Torres-Valadez R, Roman S, Ojeda-Granados C, Gonzalez-Aldaco K, Panduro A. Differential distribution of gene polymorphisms associated with hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia among Native American and Mestizo Mexicans. World J Hepatol 2022; 14:1408-1420. [PMID: 36158920 PMCID: PMC9376766 DOI: 10.4254/wjh.v14.i7.1408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 06/20/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors. The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia. AIM To define the main dyslipidemias, the frequency of lipid-related risk alleles, and their association with hyperlipidemic states among different ethnic groups in West Mexico. METHODS In a retrospective study, 1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms. Demographic, clinical, and laboratory data were collected. A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses. Genotyping was determined by allelic discrimination assay. RESULTS Hypercholesterolemia was the most prevalent dyslipidemia (42.3%). The frequency of the risk alleles associated with hypoalphalipoproteinemia (ABCA1) and hypercholesterolemia (APOE, LDLR) was higher in the Native Americans (P = 0.047). In contrast, the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia (APOE2, MTTP) (P = 0.045). In normal weight Mestizo subjects, the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia (OR = 5.33, 95%CI: 1.537-18.502, P = 0.008 and OR = 3.90, 95%CI: 1.042-14.583, P = 0.043, respectively), and displayed an increase in low-density lipoprotein cholesterol levels (APOB: β = 40.39, 95%CI: 14.415-66.366, P = 0.004; LDLR: β = 20.77, 95%CI: 5.763-35.784, P = 0.007). CONCLUSION Gene polymorphisms and dyslipidemias showed a differential distribution. Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.
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Affiliation(s)
- Rafael Torres-Valadez
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara Fray Antonio Alcalde/Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco 44280, Mexico
- Unidad Especializada en Investigación, Desarrollo e Innovación en Medicina Genómica Centro Nayarita de Innovación y Transferencia de Tecnología, Universidad Autónoma de Nayarit, Unidad Académica de Salud Integral, Tepic, Nayarit 63173, Mexico
| | - Sonia Roman
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara Fray Antonio Alcalde/Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco 44280, Mexico
| | - Claudia Ojeda-Granados
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara Fray Antonio Alcalde/Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco 44280, Mexico
| | - Karina Gonzalez-Aldaco
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara Fray Antonio Alcalde/Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco 44280, Mexico
| | - Arturo Panduro
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara Fray Antonio Alcalde/Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco 44280, Mexico
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The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population. Genes (Basel) 2020; 11:genes11101192. [PMID: 33066450 PMCID: PMC7602182 DOI: 10.3390/genes11101192] [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] [Received: 08/10/2020] [Revised: 10/05/2020] [Accepted: 10/12/2020] [Indexed: 11/17/2022] Open
Abstract
The Mexican population has one of the highest prevalences of metabolic syndrome (MetS) worldwide. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) with MetS and its components. First, we performed a pilot Genome-wide association study (GWAS) scan on a sub-sample derived from the Health Workers Cohort Study (HWCS) (n = 411). Based on GWAS results, we selected the rs1784042 and rs17120425 SNPs in the SIDT1 transmembrane family member 2 (SIDT2) gene for replication in the entire cohort (n = 1963), using predesigned TaqMan assays. We observed a prevalence of MetS in the HWCS of 52.6%. The minor allele frequency for the variant rs17120425 was 10% and 29% for the rs1784042. The SNP rs1784042 showed an overall association with MetS (OR = 0.82, p = 0.01) and with low levels of high-density lipoprotein (HDL-c) (odds ratio (OR) = 0.77, p = 0.001). The SNP rs17120425 had a significant association with type 2 diabetes (T2D) risk in the overall population (OR = 1.39, p = 0.033). Our results suggest an association of the rs1784042 and rs17120425 variants with MetS, through different mechanisms in the Mexican population. Further studies in larger samples and other populations are required to validate these findings and the relevance of these SNPs in MetS.
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Association of ABCA1 (C69T) gene polymorphism with dyslipidemia and type 2 diabetes among the Egyptian population. Meta Gene 2020. [DOI: 10.1016/j.mgene.2020.100714] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
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Fritz J, Lopez-Ridaura R, Choudhry S, Razo C, Lamadrid-Figueroa H. The association of Native American genetic ancestry and high-density lipoprotein cholesterol: A representative study of a highly admixed population. Am J Hum Biol 2020; 32:e23426. [PMID: 32329554 DOI: 10.1002/ajhb.23426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 03/11/2020] [Accepted: 04/08/2020] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE Hispanic populations typically show a high prevalence of dyslipidemias, especially of low high-density lipoproteins (HDLs) or HDL cholesterol. Highly admixed populations are ideal groups to clarify the role of genetic ancestry on HDL concentrations, isolating it from that of other factors. The objective of this study was to estimate the association between Native American genetic ancestry and HDL-cholesterol levels independent of socioeconomic factors in a representative sample of the Mexican population. METHODS We used data from the Mexican National Health Survey 2000, analyzing 1647 subjects from whom stored DNA samples and HDL measurements were available. To estimate proportional genetic ancestry (Native American, African, and European), we used a 107 genetic ancestry informative marker panel with the software STRUCTURE. To estimate the association between genetic ancestry and low HDL levels, we fitted logistic regression models with the percentage of Native American genetic ancestry, in quartiles, as the main predictor. RESULTS Mean HDL levels were 38.9 mg/dL, with 62% of subjects having levels below 40 mg/dL. Participants had on average 53.6% Native American, 39% European, and 7.3% African genetic ancestry. Those in the fourth quartile of Native American genetic ancestry had 35% higher odds of having low HDL-cholesterol relative to those in the first quartile (odds ratio, 1.35; 95% confidence interval, 0.99-1.81) after adjustment for socioeconomic level and other covariates, although the association is clearly nonlinear. CONCLUSION Native American genetic ancestry seems to play a small but distinct role in the development of low HDL cholesterol levels.
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Affiliation(s)
- Jimena Fritz
- Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico
| | - Ruy Lopez-Ridaura
- Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico
| | - Shweta Choudhry
- Human Genetics at Lung Biology Center, University of California San Francisco, San Francisco, California, USA
| | - Christian Razo
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
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Contreras-Yáñez I, Guaracha-Basáñez G, Pascual-Ramos V. Cardiovascular risk factors' behavior during the early stages of the disease, in Hispanic rheumatoid arthritis patients: a cohort study. Rheumatol Int 2019; 40:405-414. [PMID: 31606775 DOI: 10.1007/s00296-019-04451-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 09/25/2019] [Indexed: 01/27/2023]
Abstract
Rheumatoid arthritis (RA) patients from Latin America present distinctive characteristics relevant when assessing their cardiovascular (CV) risk. The objective was to monitor CV risk factor behavior in the early stages of the disease and to identify predictors of major CV outcomes (MACE). A recent-onset RA cohort was initiated in 2004; data from 185 patients with ≥ 1 year of follow-up were analyzed. Patients underwent prospective assessments of CV risk factors. Incident MACE were confirmed according to standardized definitions. Appropriated statics was used based on the distribution of the variables. At baseline, patients were primarily middle-aged females (87.6%), with active disease (69.7%). Most prevalent CV risk factors were C-reactive-protein > 1 mg/L (90.3%), Castelli ratio > 3 (83.8%), and low-high-density lipoprotein levels (73.5%). The number of patients with an incident CV risk factor after 1 year was higher for a Castelli ratio > 3 (23%), low-high-density lipoprotein serum cholesterol (16.3%), high total serum cholesterol (10.6%), and BMI ≥ 30 kg/m2 (10%). A minority of patients met the age-range criteria for the application of ACC/AHA 2013 criteria and Reynolds Risk Score (45.8% and 34.1%, respectively). Fifteen patients were classified with high-CV risk during the first year of follow-up, according to ACC/AHA 2013 criteria. Until June 2018, the cohort underwent 1358 patient/years follow-up; six patients developed incidental MACE; high-CV risk at baseline failed to predict MACE. Recent-onset RA Hispanic patients present a distinctive pattern and first-year behavior of CV risk factors. During follow-up, few patients developed incidental MACE.
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Affiliation(s)
- Irazú Contreras-Yáñez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia Belisario Domínguez, Sección XVI, CP 14080, Mexico City, Mexico
| | - Guillermo Guaracha-Basáñez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia Belisario Domínguez, Sección XVI, CP 14080, Mexico City, Mexico
| | - Virginia Pascual-Ramos
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia Belisario Domínguez, Sección XVI, CP 14080, Mexico City, Mexico.
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Ruderman A, Pérez LO, Adhikari K, Navarro P, Ramallo V, Gallo C, Poletti G, Bedoya G, Bortolini MC, Acuña-Alonzo V, Canizales-Quinteros S, Rothhammer F, Ruiz-Linares A, González-José R. Obesity, genomic ancestry, and socioeconomic variables in Latin American mestizos. Am J Hum Biol 2019; 31:e23278. [PMID: 31237064 DOI: 10.1002/ajhb.23278] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 03/29/2019] [Accepted: 05/21/2019] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. METHODS The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist-to-hip ratio and waist-to-height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well-being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. RESULTS The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. CONCLUSIONS The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values.
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Affiliation(s)
- Anahí Ruderman
- Instituto Patagónico de Ciencias Sociales y Humanas-CONICET, Puerto Madryn, Chubut, Argentina
| | - Luis O Pérez
- Instituto Patagónico de Ciencias Sociales y Humanas-CONICET, Puerto Madryn, Chubut, Argentina
| | - Kaustubh Adhikari
- School of Mathematics and Statistics, Faculty of Science, Technology, Engineering and Mathematics, The Open University, Milton Keynes, UK.,Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, UK
| | - Pablo Navarro
- Instituto Patagónico de Ciencias Sociales y Humanas-CONICET, Puerto Madryn, Chubut, Argentina
| | - Virginia Ramallo
- Instituto Patagónico de Ciencias Sociales y Humanas-CONICET, Puerto Madryn, Chubut, Argentina
| | - Carla Gallo
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Giovanni Poletti
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Gabriel Bedoya
- Grupo de Genética Molecular (GENMOL), Universidad de Antioquia, Medellín, Colombia
| | - Maria C Bortolini
- Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | | | - Samuel Canizales-Quinteros
- Unidad de Genomica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Francisco Rothhammer
- Instituto de Alta Investigación Universidad de Tarapacá, Programa de Genética Humana, ICBM Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Andres Ruiz-Linares
- Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, UK.,Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.,Laboratory of Biocultural Anthropology, Law, Ethics, and Health (Centre National de la Recherche Scientifique and Etablissement Français du Sang, UMR-7268), Aix-Marseille University, Marseille, France
| | - Rolando González-José
- Instituto Patagónico de Ciencias Sociales y Humanas-CONICET, Puerto Madryn, Chubut, Argentina
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ATP-binding cassette sub-family a member1 gene mutation improves lipid metabolic abnormalities in diabetes mellitus. Lipids Health Dis 2019; 18:103. [PMID: 31010439 PMCID: PMC6477720 DOI: 10.1186/s12944-019-0998-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 02/22/2019] [Indexed: 12/11/2022] Open
Abstract
Background Patients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients. Methods We retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI). Results A total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57–0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52–0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11–0.83, P = 0.01). Conclusions ABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients. Electronic supplementary material The online version of this article (10.1186/s12944-019-0998-3) contains supplementary material, which is available to authorized users.
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Aguirre M, Briceño Y, Gómez-Pérez R, Zerpa Y, Camacho N, Paoli M. Triglycerides/High density lipoprotein cholesterol ratio as a cardiometabolic risk marker in children and adolescents from Mérida city, Venezuela. ENDOCRINOL DIAB NUTR 2018; 65:74-83. [PMID: 29290474 DOI: 10.1016/j.endinu.2017.10.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/21/2017] [Accepted: 10/28/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVE To determine the behavior of the triglycerides/HDL-cholesterol ratio (TG/HDL) as a cardiometabolic risk marker in children and adolescents from Mérida, Venezuela. METHODS A total of 1292 children and adolescents aged 7-18 years who attended educational institutions in the Libertador Municipality were enrolled into this study. Anthropometric measurements and blood pressure values were recorded. Fasting blood glucose, insulin and lipid levels were measured. The TG/HDL ratio, HOMA-IR, and QUICKI indexes were calculated. Subjects were categorized as with and without cardiometabolic risk based on the presence or absence of 2or more risk factors. Cut-off points for the TG/HDL ratio were determined by constructing ROC curves. RESULTS Significantly higher mean TG/HDL ratios were found in pubertal (2.2 ± 1.7) as compared to prepubertal subjects (1.8 ± 1.5; P=.001), with no sex differences. Two or more risk factors were found in 14.7% (n=192) of the participants, in whom TG/HDL ratios were significantly higher as compared to those with no risk (3.5±2.9 versus 1.6±0.8 in prepubertal and 4.1 ± 3.5 versus 1.8 ± 0.9 in pubertal subjects; P=.0001). According to cardiometabolic risk, cut-off points for the TG/HDL ratio of 1.8 and 2.5 were found for prepubertal and pubertal children respectively. These cut-off points showed risks (odds ratio) higher than 2.5 for conditions such as metabolic syndrome, elevated non-HDL-C, abdominal obesity, and elevated HOMA-IR. CONCLUSION In this sample of children and adolescents, an elevated TG/HDLc ratio was found to be a good marker for predicting cardiometabolic risk.
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Affiliation(s)
- Miguel Aguirre
- Centro de Investigaciones Endocrino-Metabólicas Dr. Félix Gómez, Facultad de Medicina, Universidad del Zulia, Servicio de Endocrinología, Hospital Universitario de Maracaibo, Maracaibo, Estado Zulia, Venezuela
| | - Yajaira Briceño
- Unidad de Endocrinología, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela
| | - Roald Gómez-Pérez
- Unidad de Endocrinología, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela
| | - Yajaira Zerpa
- Unidad de Endocrinología, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela
| | - Nolis Camacho
- Unidad de Nutrición, Crecimiento y Desarrollo Infantil, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela
| | - Mariela Paoli
- Unidad de Endocrinología, Instituto Autónomo Hospital Universitario de Los Andes, Universidad de Los Andes, Mérida, Venezuela.
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Ponte-Negretti CI, Isea-Perez JE, Lorenzatti AJ, Lopez-Jaramillo P, Wyss-Q FS, Pintó X, Lanas F, Medina J, Machado-H LT, Acevedo M, Varleta P, Bryce A, Carrera C, Peñaherrera CE, Gómez-M JR, Lozada A, Merchan-V A, Piskorz D, Morales E, Paniagua M, Medina-Palomin F, Villar-M RA, Cobos L, Gómez-Alvares E, Alonso R, Colan J, Chirinos J, Lara J, Ullauri V, Arocha I. Atherogenic Dyslipidemia in Latin America: Prevalence, causes and treatment: Expert's position paper made by The Latin American Academy for the Study of Lipids (ALALIP) Endorsed by the Inter-American Society of Cardiology (IASC), the South American Society of Cardiology (SSC), the Pan-American College of Endothelium (PACE), and the International Atherosclerosis Society (IAS). Int J Cardiol 2017; 243:516-522. [PMID: 28552520 DOI: 10.1016/j.ijcard.2017.05.059] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 05/15/2017] [Indexed: 12/12/2022]
Abstract
This is an executive summary made by a group of experts named Latin American Academy for the study of Lipids (ALALIP). In the current clinical guidelines, atherogenic dyslipidemia (AD) is a poorly recognized entity. Due to the frequent lipid alterations associated with AD in Latin America (LA), we organized a group of experts named (ALALIP) to generate a document in order to analyze their prevalence and to offer practical recommendations. METHODOLOGY using the Delphi methodology, we conducted a comprehensive literature review with emphasis on those publications related to LA. Subsequently, we developed key questions for discussion. As a convention, those recommendations that had a 100% of acceptance were considered unanimous, those with >80% were consensual, and those with <80% were in disagreement. RESULTS a systematic analysis of national health surveys and regional cohort studies showed a consistently high prevalence of the lipid abnormalities that define AD: low levels of high-density lipoprotein cholesterol (HDL-C) range from 34.1% to 53.3% and elevated triglycerides (TG) range from 25.5% to 31.2%. These abnormalities could be related to high consumption of food with a high caloric density, cholesterol and trans fats, a sedentary lifestyle and perhaps epigenetic changes CONCLUSIONS: lipid abnormalities that define AD have a high prevalence in LA. The interaction between an unfavorable lifestyle, inheritance and epigenetic changes is probably their cause. It is important to design a global study of risk factors in LA to know its true prevalence in the region, its consequences and to derive from its treatment strategies.
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Rodríguez A, Gonzalez L, Ko A, Alvarez M, Miao Z, Bhagat Y, Nikkola E, Cruz-Bautista I, Arellano-Campos O, Muñoz-Hernández LL, Ordóñez-Sánchez ML, Rodriguez-Guillen R, Mohlke KL, Laakso M, Tusie-Luna T, Aguilar-Salinas CA, Pajukanta P. Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene. Arterioscler Thromb Vasc Biol 2016; 36:1350-5. [PMID: 27199446 PMCID: PMC5154300 DOI: 10.1161/atvbaha.116.307182] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 05/09/2016] [Indexed: 11/16/2022]
Abstract
OBJECTIVE We recently identified a locus on chromosome 18q11.2 for high serum triglycerides in Mexicans. We hypothesize that the lead genome-wide association study single-nucleotide polymorphism rs9949617, or its linkage disequilibrium proxies, regulates 1 of the 5 genes in the triglyceride-associated region. APPROACH AND RESULTS We performed a linkage disequilibrium analysis and found 9 additional variants in linkage disequilibrium (r(2)>0.7) with the lead single-nucleotide polymorphism. To select the variants for functional analyses, we annotated the 10 variants using DNase I hypersensitive sites, transcription factor and chromatin states and identified rs17259126 as the lead candidate variant for functional in vitro validation. Using luciferase transcriptional reporter assay in liver HepG2 cells, we found that the G allele exhibits a significantly lower effect on transcription (P<0.05). The electrophoretic mobility shift and ChIPqPCR (chromatin immunoprecipitation coupled with quantitative polymerase chain reaction) assays confirmed that the minor G allele of rs17259126 disrupts an hepatocyte nuclear factor 4 α-binding site. To find the regional candidate gene, we performed a local expression quantitative trait locus analysis and found that rs17259126 and its linkage disequilibrium proxies alter expression of the regional transmembrane protein 241 (TMEM241) gene in 795 adipose RNAs from the Metabolic Syndrome In Men (METSIM) cohort (P=6.11×10(-07)-5.80×10(-04)). These results were replicated in expression profiles of TMEM241 from the Multiple Tissue Human Expression Resource (MuTHER; n=856). CONCLUSIONS The Mexican genome-wide association study signal for high serum triglycerides on chromosome 18q11.2 harbors a regulatory single-nucleotide polymorphism, rs17259126, which disrupts normal hepatocyte nuclear factor 4 α binding and decreases the expression of the regional TMEM241 gene. Our data suggest that decreased transcript levels of TMEM241 contribute to increased triglyceride levels in Mexicans.
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Affiliation(s)
- Alejandra Rodríguez
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Luis Gonzalez
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Arthur Ko
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Marcus Alvarez
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Zong Miao
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Yash Bhagat
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Elina Nikkola
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Ivette Cruz-Bautista
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Olimpia Arellano-Campos
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Linda L Muñoz-Hernández
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Maria-Luisa Ordóñez-Sánchez
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Rosario Rodriguez-Guillen
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Karen L Mohlke
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Markku Laakso
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Teresa Tusie-Luna
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Carlos A Aguilar-Salinas
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.)
| | - Päivi Pajukanta
- From the Department of Human Genetics, David Geffen School of Medicine (A.R., L.G., A.K., M.A., Z.M., Y.B., E.N., P.P.), Molecular Biology Institute (A.K., P.P.), and Bioinformatics Interdepartmental Program (P.P.), University of California, Los Angeles; Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, Mexico City, Mexico (I.C.-B., O.A.-C., L.L.M.-H., M.-L. O.-S., R.R.-G., T.T.-L., C.A.A.-S.); Department of Genetics, University of North Carolina, Chapel Hill (K.L.M.); Department of Medicine, University of Eastern Finland and Kuopio University Hospital (M.L.); and Instituto de Investigaciones Biomédicas de la UNAM, Mexico City, Mexico (T.T.-L.).
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14
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An Evolutionary Perspective of Nutrition and Inflammation as Mechanisms of Cardiovascular Disease. INTERNATIONAL JOURNAL OF EVOLUTIONARY BIOLOGY 2015; 2015:179791. [PMID: 26693381 PMCID: PMC4677015 DOI: 10.1155/2015/179791] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 11/12/2015] [Indexed: 01/11/2023]
Abstract
When cardiovascular diseases are viewed from an evolutionary biology perspective, a heightened thrifty and an inflammatory design could be their mechanisms. Human ancestors confronted a greater infectious load and were subjected to the selection for proinflammatory genes and a strong inflammatory function. Ancestors also faced starvation periods that pressed for a thrifty genotype which caused fat accumulation. The pressure of sustaining gluconeogenesis during periods of poor nourishment selected individuals with insulin resistance. Obesity induces a proinflammatory state due to the secretion of adipokines which underlie cardiometabolic diseases. Our actual lifestyle needs no more of such proinflammatory and thrifty genotypes and these ancestral genes might increase predisposition to diseases. Risk factors for atherosclerosis and diabetes are based on inflammatory and genetic foundations that can be accounted for by excess fat. Longevity has also increased in recent times and is related to a proinflammatory response with cardiovascular consequences. If human ancestral lifestyle could be recovered by increasing exercise and adapting a calorie restriction diet, obesity would decrease and the effects on chronic low-grade inflammation would be limited. Thereby, the rates of both atherosclerosis and diabetes could be reduced.
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15
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Lara-Riegos JC, Ortiz-López MG, Peña-Espinoza BI, Montúfar-Robles I, Peña-Rico MA, Sánchez-Pozos K, Granados-Silvestre MA, Menjivar M. Diabetes susceptibility in Mayas: Evidence for the involvement of polymorphisms in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes. Gene 2015; 565:68-75. [PMID: 25839936 DOI: 10.1016/j.gene.2015.03.065] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 03/13/2015] [Accepted: 03/29/2015] [Indexed: 01/11/2023]
Abstract
Association of type 2 diabetes (T2D) with common variants in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes have been reported, mainly in populations of European and Asian ancestry and to a lesser extent in Latin Americans. Thus, we aimed to investigate the contribution of rs1111875 (HHEX), rs1800961 (HNF4α), rs5219 (KCNJ11), rs1801282 (PPARγ), rs10811661 (CDKN2A/2B), rs13266634 (SLC30A8), rs12779790 (CDC123/CAMK1D), rs7903146 (TCF7L2), rs9282541 (ABCA1) and rs13342692 (SLC16A11) polymorphisms in the genetic background of Maya population to associate their susceptibility to develop T2D. This is one of the first studies designed specifically to investigate the inherited component of T2D in the indigenous population of Mexico. SNPs were genotyped by allelic discrimination method in 575 unrelated Maya individuals. Two SNPs rs10811661 and rs928254 were significantly associated with T2D after adjusting for BMI; rs10811661 in a recessive and rs9282541 in a dominant model. Additionally, we found phenotypical alterations associated with genetic variants: HDL to rs9282541 and insulin to rs13342692. In conclusion, these findings support an association of genetic polymorphisms to develop T2D in Maya population.
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Affiliation(s)
- J C Lara-Riegos
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México - Instituto Nacional de Medicina Genómica, Mexico
| | - M G Ortiz-López
- Laboratory of Molecular Endocrinology, Hospital Juárez de México, Mexico
| | - B I Peña-Espinoza
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México - Instituto Nacional de Medicina Genómica, Mexico
| | - I Montúfar-Robles
- Laboratory of Molecular Endocrinology, Hospital Juárez de México, Mexico
| | - M A Peña-Rico
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México - Instituto Nacional de Medicina Genómica, Mexico
| | - K Sánchez-Pozos
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México - Instituto Nacional de Medicina Genómica, Mexico
| | - M A Granados-Silvestre
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México - Instituto Nacional de Medicina Genómica, Mexico
| | - M Menjivar
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México - Instituto Nacional de Medicina Genómica, Mexico.
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Amerindian-specific regions under positive selection harbour new lipid variants in Latinos. Nat Commun 2014; 5:3983. [PMID: 24886709 PMCID: PMC4062071 DOI: 10.1038/ncomms4983] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 04/29/2014] [Indexed: 12/13/2022] Open
Abstract
Dyslipidemia and obesity are especially prevalent in populations with Amerindian
backgrounds, such as Mexican–Americans, which predispose these populations to
cardiovascular disease. Here we design an approach, known as the cross-population allele
screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273
Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing
CPAS to restrict the GWAS input variants to only those differing in frequency between the
two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase
3 (SIK3), and three
loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein
A5 (APOA5)
harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we
observe that SIK3 and one novel
lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal,
the SIK3 risk variant carriers
display high triglyceride levels. These findings suggest that Amerindian-specific genetic
architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans. Dyslipidemia and obesity have a high prevalence in populations with
Amerindian backgrounds, such as Mexican–Americans. Here, the authors design an approach
to identify Amerindian risk genes in Mexicans and identify five genomic loci, which include
RORA and SIK3 that may contribute to the risk of dyslipidemia and obesity in
Amerindian populations.
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A Framework to Examine the Role of Epigenetics in Health Disparities among Native Americans. Nurs Res Pract 2013; 2013:410395. [PMID: 24386563 PMCID: PMC3872279 DOI: 10.1155/2013/410395] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Revised: 11/06/2013] [Accepted: 11/19/2013] [Indexed: 12/29/2022] Open
Abstract
Background. Native Americans disproportionately experience adverse childhood experiences (ACEs) as well as health disparities, including high rates of posttraumatic stress, depression, and substance abuse. Many ACEs have been linked to methylation changes in genes that regulate the stress response, suggesting that these molecular changes may underlie the risk for psychiatric disorders related to ACEs. Methods. We reviewed published studies to provide evidence that ACE-related methylation changes contribute to health disparities in Native Americans. This framework may be adapted to understand how ACEs may result in health disparities in other racial/ethnic groups. Findings. Here we provide evidence that links ACEs to methylation differences in genes that regulate the stress response. Psychiatric disorders are also associated with methylation differences in endocrine, immune, and neurotransmitter genes that serve to regulate the stress response and are linked to psychiatric symptoms and medical morbidity. We provide evidence linking ACEs to these epigenetic modifications, suggesting that ACEs contribute to the vulnerability for developing psychiatric disorders in Native Americans. Conclusion. Additional studies are needed to better understand how ACEs contribute to health and well-being. These studies may inform future interventions to address these serious risks and promote the health and well-being of Native Americans.
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Aguilar-Salinas CA, Muñoz-Hernandez LL, Cobos-Bonilla M, Ramírez-Márquez MR, Ordoñez-Sanchez ML, Mehta R, Medina-Santillan R, Tusie-Luna MT. The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus. Metabolism 2013; 62:638-41. [PMID: 23273975 DOI: 10.1016/j.metabol.2012.11.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Revised: 11/15/2012] [Accepted: 11/20/2012] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program. Each person with the risk allele (R230C) was matched by age, gender and BMI to three others with the wild type variant (R230R). Following a four week stabilization period, only participants with a greater than 70% adherence to metformin and a stable body weight were prescribed glyburide therapy for a further 16 weeks. The main outcome variable was the glyburide dose required to achieve treatment goals. RESULTS No significant difference was observed in the glucose lowering effect of glyburide between subjects with the R230C and R230R alleles. However, the dose of sulfonylurea was significantly higher in the R230C participants compared with the R230R subjects (3.3±2.1 vs 6.3±5 mg/day, p<0.001). A higher percentage of R230C participants required at least 5mg of glyburide per day to achieve treatment goals. The glyburide dose was determined by the presence of the risk allele, among other factors. CONCLUSIONS Patients with type 2 diabetes who have the R230C allele of ABCA1 needed a higher dose of glyburide in order to achieve the same glucose lowering effect as that in persons with the wild type variant.
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Affiliation(s)
- Carlos A Aguilar-Salinas
- Department of Endocrinology and Metabolism. Instituto Nacional de Ciencias Médicas y Nutrición. México City, México.
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Hirschler V, Maccallini G, Aranda C, Molinari C. Dyslipidemia without obesity in indigenous Argentinean children living at high altitude. J Pediatr 2012; 161:646-51.e1. [PMID: 22658786 DOI: 10.1016/j.jpeds.2012.04.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Revised: 02/15/2012] [Accepted: 04/11/2012] [Indexed: 01/09/2023]
Abstract
OBJECTIVES To compare the prevalence of cardiovascular disease risk factors in Indian children from San Antonio de los Cobres (SAC) and children from Buenos Aires (BA), and to examine body mass index (BMI), waist circumference (WC), and WC/height as predictors of dyslipidemia in both groups. STUDY DESIGN Data were collected cross-sectionally from BMI, WC, blood pressure, Tanner scale, glucose, lipids, and insulin. Dyslipidemia was defined by the National Cholesterol Education Program and American Heart Association. RESULTS The mean ages were 10.6 ± 3.0 and 9.5 ± 2.0 years in SAC vs BA children. Of the 330 SAC children, 15 (4.5%) were overweight and 12 (3.6%) obese, and of the 603 BA, 97 (16.1%) were overweight and 82 (13.6%) obese per Centers for Disease Control. There was a significantly higher prevalence of high triglycerides (28.8% vs 3.5%) and low high-density lipoprotein cholesterol (30.0% vs 5.5%) in SAC vs BA children. The areas under the receiver operating characteristic curve in predicting high triglycerides were BMI = 0.55 (95% CI, 0.48-0.62; P = .15) in SAC and BMI = 0.65 (95% CI, 0.52-0.77; P = .02) in BA children. Similar results from the areas under the receiver operating characteristic curve were obtained when low high-density lipoprotein cholesterol was used, indicating that BMI was not a significant predictor for dyslipidemia in SAC children. When BMI was replaced by WC and WC/height, results were similar. CONCLUSIONS Anthropometric markers were not an acceptable predictor for National Cholesterol Education Program cutoffs for dyslipidemia in SAC children. Longitudinal studies should determine if SAC children are at high risk for cardiovascular diseases because of genetic background.
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20
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Lifestyle behaviors and dyslipidemia in Argentinean native versus urban children. Clin Biochem 2012; 45:1161-6. [DOI: 10.1016/j.clinbiochem.2012.04.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Revised: 04/21/2012] [Accepted: 04/24/2012] [Indexed: 01/18/2023]
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Romero-Hidalgo S, Villarreal-Molina T, González-Barrios JA, Canizales-Quinteros S, Rodríguez-Arellano ME, Yañez-Velazco LB, Bernal-Alcantara DA, Villa AR, Antuna-Puente B, Acuña-Alonzo V, Merino-García JL, Moreno-Sandoval HN, Carnevale A. Carbohydrate intake modulates the effect of the ABCA1-R230C variant on HDL cholesterol concentrations in premenopausal women. J Nutr 2012; 142:278-83. [PMID: 22190032 DOI: 10.3945/jn.111.152421] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State's Employees' Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.
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Affiliation(s)
- Sandra Romero-Hidalgo
- Computational Genomics Department, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
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RÍOS-GONZÁLEZ BLANCAE, LUÉVANO-ORTEGA KARLAE, SALDAÑA-CRUZ ANAM, GONZÁLEZ-GARCÍA JUANR, MAGAÑA-TORRES MARÍATERESA. Polymorphisms of seven genes involved in lipid metabolism in an unselected Mexican population. J Genet 2011. [DOI: 10.1007/s12041-011-0118-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Aguilar-Salinas CA, Canizales-Quinteros S, Rojas-Martínez R, Mehta R, Rodriguez-Guillén R, Ordoñez-Sanchez ML, Riba L, Tusié-Luna MT. The non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 is associated with low HDL cholesterol concentrations in Mexican adults: a population based nation wide study. Atherosclerosis 2011; 216:146-50. [PMID: 21315358 DOI: 10.1016/j.atherosclerosis.2010.10.049] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2010] [Revised: 09/24/2010] [Accepted: 10/05/2010] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To search for an association between the non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 and low HDL cholesterol levels in a Mexican, population-based nation wide survey. METHODS The 2000 National Health Survey is a cross sectional study that included individuals from 400 cities. All individuals who had a 9-12-h fasted blood sample and a DNA sample were selected (n = 1729). These cases were randomly distributed; no bias was detected for sex, education, region or socioeconomic status. The R230C variant was genotyped using TaqMan assays. RESULTS In individuals with the R230C/C230C genotypes (39.03 mg/dl (36.63-41.43)) lower HDL-C levels (p < 0.001) were observed compared to those with the R230R genotype (44.7 mg/dl (43.31-46.24)). The difference remained significant after adjusting for gender, body mass index and waist circumference; the mean difference in HDL cholesterol levels between alleles was 5.73 ± 1.4 mg/dl. The magnitude of the effect was significantly greater in males. The C230 allele of ABCA1 was associated with an increased risk for hypoalphalipoproteinemia (OR 1.66 (95%CI 1.08-2.54), p < 0.05). The population attributable risk (PAR) for having hypoalphalipoproteinemia of the C230 allele of the ABCA1, after considering the confounding effect of waist circumference and gender, was 12.2% (95%CI 1.4-24.2%). CONCLUSION The non-synonymous Arg230Cys variant of ABCA1 is associated with low levels of HDL cholesterol levels in Mexican adults. The HDL cholesterol lowering effect of the variant is greater in males. The size of the effect is greater compared to that reported for other ABCA1 variants.
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Affiliation(s)
- Carlos A Aguilar-Salinas
- Departamento de Endocrinología y Metabolismo del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Mexico14000 DF, Mexico.
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Weissglas-Volkov D, Pajukanta P. Genetic causes of high and low serum HDL-cholesterol. J Lipid Res 2010; 51:2032-57. [PMID: 20421590 DOI: 10.1194/jlr.r004739] [Citation(s) in RCA: 155] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Plasma levels of HDL cholesterol (HDL-C) have a strong inherited basis with heritability estimates of 40-60%. The well-established inverse relationship between plasma HDL-C levels and the risk of coronary artery disease (CAD) has led to an extensive search for genetic factors influencing HDL-C concentrations. Over the past 30 years, candidate gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identified several genetic variations for plasma HDL-C levels. However, the functional role of several of these variants remains unknown, and they do not always correlate with CAD. In this review, we will first summarize what is known about HDL metabolism, monogenic disorders associated with both low and high HDL-C levels, and candidate gene studies. Then we will focus this review on recent genetic findings from the GWA studies and future strategies to elucidate the remaining substantial proportion of HDL-C heritability. Comprehensive investigation of the genetic factors conferring to low and high HDL-C levels using integrative approaches is important to unravel novel pathways and their relations to CAD, so that more effective means of diagnosis, treatment, and prevention will be identified.
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Acuña-Alonzo V, Flores-Dorantes T, Kruit JK, Villarreal-Molina T, Arellano-Campos O, Hünemeier T, Moreno-Estrada A, Ortiz-López MG, Villamil-Ramírez H, León-Mimila P, Villalobos-Comparan M, Jacobo-Albavera L, Ramírez-Jiménez S, Sikora M, Zhang LH, Pape TD, Granados-Silvestre MDA, Montufar-Robles I, Tito-Alvarez AM, Zurita-Salinas C, Bustos-Arriaga J, Cedillo-Barrón L, Gómez-Trejo C, Barquera-Lozano R, Vieira-Filho JP, Granados J, Romero-Hidalgo S, Huertas-Vázquez A, González-Martín A, Gorostiza A, Bonatto SL, Rodríguez-Cruz M, Wang L, Tusié-Luna T, Aguilar-Salinas CA, Lisker R, Moises RS, Menjivar M, Salzano FM, Knowler WC, Bortolini MC, Hayden MR, Baier LJ, Canizales-Quinteros S. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans. Hum Mol Genet 2010; 19:2877-85. [PMID: 20418488 DOI: 10.1093/hmg/ddq173] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.
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Affiliation(s)
- Víctor Acuña-Alonzo
- Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Universidad Nacional Autónoma de México, Mexico City 14000, Mexico
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