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Idris AB, Idris AB, Gumaa MA, Idris MB, Elgoraish A, Mansour M, Allam D, Arbab BMO, Beirag N, Ibrahim EAM, Hassan MA. Identification of functional tumor necrosis factor-alpha promoter variants associated with Helicobacter pylori infection in the Sudanese population: Computational approach. World J Gastroenterol 2022; 28:242-262. [PMID: 35110948 PMCID: PMC8776532 DOI: 10.3748/wjg.v28.i2.242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/13/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a ubiquitous bacterium that affects nearly half of the world's population with a high morbidity and mortality rate. Polymorphisms within the tumor necrosis factor-alpha (TNF-A) promoter region are considered a possible genetic basis for this disease. AIM To functionally characterize the genetic variations in the TNF-A 5'-region (-584 to +107) of Sudanese patients infected with H. pylori using in silico tools. METHODS An observational study was carried out in major public and private hospitals in Khartoum state. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy. Genomic DNA was extracted. Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H. pylori infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of TNF-A in H. pylori-infected patients. Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region. A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation. Also, a multivariate logistic regression model was constructed to estimate odds ratios and their 95% confidence intervals for the association between TNF-A-1030, sociodemographic characteristics and H. pylori infection. Differences were statistically significant if P < 0.05. Statistical analyses were performed using Stata version 11 software. RESULTS A total of seven single nucleotide polymorphisms were observed in the TNF-A 5'-region of Sudanese patients infected with H. pylori. Only one of them (T > A, -76) was located at the in silico-predicted promoter region (-146 to +10), and it was predicted to alter transcription factor binding sites and composite regulatory elements. A novel mutation (A > T, +27) was detected in the 5' untranslated region, and it could affect the post-transcriptional regulatory pathways. Genotyping of TNF-A-1030 showed a lack of significant association between -1030T and susceptibility to H. pylori and gastric cancer in the studied population (P = 0.1756) and (P = 0.8116), respectively. However, a significant association was detected between T/C genotype and H. pylori infection (39.34% vs 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, P = 0.020). Mammalian conservation was observed for the (-146 to +10) region in chimpanzee (99.4%), rhesus monkey (95.6%), cow (91.8%), domesticated dog (89.3%), mouse (84.3%), rat (82.4%) and opossum (78%). CONCLUSION Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.
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Affiliation(s)
- Abeer Babiker Idris
- Department of Agricultural Science and Technology, Institute of Natural and Applied Sciences, Erciyes University, Kayseri 38039, Turkey
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum 11111, Sudan.
| | - Alaa B Idris
- Department of Neurosurgery, Ribat University Hospital, Khartoum 11111, Sudan
| | - Manal A Gumaa
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum 11111, Sudan
| | - Mohammed Babiker Idris
- BioMérieux Clinical and Application Advisor, Al-Jeel Medical Co., Riyadh 11422, Saudi Arabia
| | - Amanda Elgoraish
- Department of Epidemiology, Tropical Medicine Research Institute, Khartoum 11111, Sudan
| | - Mohamed Mansour
- Department of Gastroenterology, Ibn Sina Specialized Hospital, Khartoum 11111, Sudan
| | - Dalia Allam
- Department of Gastroenterology, Ibn Sina Specialized Hospital, Khartoum 11111, Sudan
| | - Bashir MO Arbab
- Department of Gastroenterology, Modern Medical Centre, Khartoum 11111, Sudan
| | - Nazar Beirag
- Biosciences, College of Health, Medicine and Life Sciences, Brunel University, London UB8 3PH, Uxbridge, United Kingdom
| | - El-Amin M Ibrahim
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum 11111, Sudan
| | - Mohamed A Hassan
- Department of Bioinformatics, Africa city of technology, Khartoum 11111, Sudan
- Department of Bioinformatics, DETAGEN Genetic Diagnostics Center, Kayseri 38350, Turkey
- Department of Translation Bioinformatics, Detavax Biotech, Kayseri 38350, Turkey
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Systematic review and meta-analysis of association of polymorphisms in inflammatory cytokine genes with coronary artery disease. Inflamm Res 2020; 69:1001-1013. [PMID: 32719924 DOI: 10.1007/s00011-020-01385-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/09/2020] [Accepted: 07/22/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND It has comprehensively been acknowledged that a genetic contribution, especially in immune inflammatory players, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are critically involved in the pathophysiology of coronary artery disease (CAD). This meta-analysis study aimed to reach a conclusive understanding of the role of genetic polymorphisms, including IL6 gene C572G (rs1800796) and G174C (rs1800795) as well as TNFA gene G238A (rs361525) and G308A (rs1800629) in susceptibility to CAD. METHODS Two major databases, namely MEDLINE and Scopus, were searched to find the studies surveying the mentioned polymorphisms and CAD susceptibility up to July 2020. Association comparison between the polymorphisms and CAD susceptibility were assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). RESULTS This meta-analysis study was conducted on 69 papers (73 population studies), comprising 5062 patients and 8446 controls for IL6 gene rs1800796 (17 studies), 13801 patients and 16215 controls for IL6 gene rs1800795 (38 studies), 1439 patients and 2850 controls for TNFA gene rs361525 (5 studies), and 5051 patients and 3958 controls for TNFA gene rs1800629 (13 studies), according to inclusion and exclusion criteria. There were statistically positive association between all genetic comparisons of IL6 gene rs1800795 polymorphism and the CAD risk. Moreover, the recessive model (CC vs. CG + GG) in IL6 gene rs1800796 polymorphism had marginally significant association with decreased risk of CAD. None of the TNFA gene polymorphisms were associated with CAD risk. CONCLUSIONS The meta-analysis revealed the positive association of IL6 gene rs1800795 polymorphism in susceptibility to CAD.
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van der Houwen T, van Laar J. Behҫet's Disease, and the Role of TNF-α and TNF-α Blockers. Int J Mol Sci 2020; 21:E3072. [PMID: 32349254 PMCID: PMC7246873 DOI: 10.3390/ijms21093072] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 04/22/2020] [Accepted: 04/24/2020] [Indexed: 12/14/2022] Open
Abstract
In this both narrative and systematic review, we explore the role of TNF-α in the immunopathogenesis of Behçet's disease (BD) and the effect of treatment with TNF-α blockers. BD is an auto-inflammatory disease, characterized by recurrent painful oral ulcerations. The pathogenesis of BD is not yet elucidated; it is assumed that TNF-α may play a key role. In the narrative review, we report an increased production of TNF-α, which may be stimulated via TLR-signaling, or triggered by increased levels of IL-1β and IFN-γ. The abundance of TNF-α is found in both serum and in sites of inflammation. This increased presence of TNF-α stimulates T-cell development toward pro-inflammatory subsets, such as Th17 and Th22 cells. Treatment directed against the surplus of TNF-α is investigated in the systematic review, performed according to the PRISMA guideline. We searched the Pubmed and Cochrane database, including comparative studies only. After including 11 studies, we report a beneficial effect of treatment with TNF-α blockers on the various manifestations of BD. In conclusion, the pivotal role of TNF-α in the immunopathogenesis of BD is reflected in both the evidence of their pro-inflammatory effects in BD and in the evidence of the positive effect of treatment on the course of disease in BD.
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Affiliation(s)
| | - Jan van Laar
- Section of Clinical Immunology, Departments of Internal Medicine and Immunology, ErasmusMC, 3015 GD Rotterdam, The Netherlands;
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Seeger AY, Ringling MD, Zohair H, Blanke SR. Risk factors associated with gastric malignancy during chronic Helicobacter pylori Infection. MEDICAL RESEARCH ARCHIVES 2020; 8:2068. [PMID: 37655156 PMCID: PMC10470974 DOI: 10.18103/mra.v8i3.2068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Chronic Helicobacter pylori (Hp) infection is considered to be the single most important risk factor for the development of gastric adenocarcinoma in humans, which is a leading cause of cancer-related death worldwide. Nonetheless, Hp infection does not always progress to malignancy, and, gastric adenocarcinoma can occur in the absence of detectable Hp carriage, highlighting the complex and multifactorial nature of gastric cancer. Here we review known contributors to gastric malignancy, including Hp virulence factors, host genetic variation, and multiple environmental variables. In addition, we assess emerging evidence that resident gastric microflora in humans might impact disease progression in Hp-infected individuals. Molecular approaches for microbe identification have revealed differences in the gastric microbiota composition between cancer and non-cancerous patients, as well as infected and uninfected individuals. Although the reasons underlying differences in microbial community structures are not entirely understood, gastric atrophy and hypochlorhydria that accompany chronic Hp infection may be a critical driver of gastric dysbiosis that promote colonization of microbes that contribute to increased risk of malignancy. Defining the importance and role of the gastric microbiota as a potential risk factor for Hp-associated gastric cancer is a vital and exciting area of current research.
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Affiliation(s)
- Ami Y. Seeger
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| | - Megan D. Ringling
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| | - Huzaifa Zohair
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
| | - Steven R. Blanke
- Department of Microbiology, School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
- Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
- Biomedical and Translational Sciences Department, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801
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Chen TH, Huang JJ, Kung WS, Lee SS, Sun HY, Chuang HY. The Association of Serum TNF-α Levels and Blood Multi-Elements Modified by TNF-α Gene Polymorphisms in Metal Industrial Workers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16214079. [PMID: 31652851 PMCID: PMC6862333 DOI: 10.3390/ijerph16214079] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 10/17/2019] [Accepted: 10/18/2019] [Indexed: 12/27/2022]
Abstract
Health of the metal industrial workers should be a noteworthy issue due to the hazard of chronic exposure to metals or toxic elements. The interactions among multiple elements are sophisticated and may differ from person to person. Tumor necrosis factor-α (TNF-α) gene polymorphisms were supposed to be involved with the interactions because TNF-α plays an important role in inflammation, a mechanism by which toxic elements cause threats to human health. This research aimed to analyze the influence of TNF-α gene polymorphisms and multi-elements on serum TNF-α level. Blood multi-elements concentrations (lead, cadmium, arsenic, selenium, cobalt, copper, and zinc), serum TNF-α level, and TNF-α single nucleotide polymorphisms (SNPs), including −238G > A (rs361525), −308G > A (rs1800629), −857C > T (rs1799724), −863C > A (rs1800630), and −1031T > C (rs1799964), were measured in 462 metal industrial workers. We applied mixed-effect models to analyze the interactions among multi-elements and TNF-α SNPs. Blood concentration of all elements were positively associated with serum TNF-α level, and the effects may be modified by TNF-α gene polymorphisms. Our study revealed that TNF-α −308A/A and −1031C/C may be susceptible genotypes, and thus we suggest that those workers should take preventive measures against metal toxicity.
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Affiliation(s)
- Tzu-Hua Chen
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan.
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan .
| | - Joh-Jong Huang
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan .
| | - Wei-Shyang Kung
- Department of Pediatrics, National Cheng Kung University Hospital, Tainan 70101, Taiwan.
| | - Su-Shin Lee
- Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Hung-Yu Sun
- Department of Family Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan.
| | - Hung-Yi Chuang
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
- Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
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A biocultural approach to psychiatric illnesses. Psychopharmacology (Berl) 2019; 236:2923-2936. [PMID: 30721322 DOI: 10.1007/s00213-019-5178-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 01/21/2019] [Indexed: 12/13/2022]
Abstract
RATIONALE As a species, humans are vulnerable to numerous mental disorders, including depression and schizophrenia. This susceptibility may be due to the evolution of our large, complex brains, or perhaps because these illnesses counterintuitively confer some adaptive advantage. Additionally, cultural and biological factors may contribute to susceptibility and variation in mental illness experience and expression. Taking a holistic perspective could strengthen our understanding of these illnesses in diverse cultural contexts. OBJECTIVES This paper reviews some of these potential factors and contextualizes mental disorders within a biocultural framework. RESULTS There is growing evidence that suggests cultural norms may influence inflammation, neurotransmitters, and neurobiology, as well as the illness experience. Specific examples include variation in schizophrenia delusions between countries, differences in links between inflammation and emotion between the United States and Japan, and differences in brain activity between Caucasian and Asian participants indicating that cultural values may moderate cognitive processes related to social cognition and interoception. CONCLUSIONS Research agendas that are grounded in an appreciation of biocultural diversity as it relates to psychiatric illness represent key areas for truly interdisciplinary research that can result in culturally sensitive treatments and highlight possible biological variation affecting medical treatment.
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Passan S, Goyal S, Bhat MA, Singh D, Vanita V. Association of TNF-α gene alterations (c.-238G>A, c.-308G>A, c.-857C>T, c.-863C>A) with primary glaucoma in north Indian cohort. Gene 2019; 709:25-35. [PMID: 31132515 DOI: 10.1016/j.gene.2019.05.035] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 04/27/2019] [Accepted: 05/17/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND Tumor Necrosis Factor-alpha (TNF-α) a pleuripotent pro-inflammatory cytokine, is involved in retinal ganglion cells apoptosis in glaucoma. Thus present study aimed to analyze the association of TNF-α promoter region alterations (c.-238G>A (rs361525), c.-308G>A (rs1800629), c.-857C>T (rs1799724) and c.-863C>A (rs1800630)) with glaucoma in north Indian cohort. METHODS Present hospital based case control study involved 286 glaucoma patients (Primary Open Angle Glaucoma [POAG], Primary Angle Closure Glaucoma [PACG], Primary Congenital Glaucoma [PCG]) and 300 controls. TNF-α gene alteration (c.-238G>A (also referred as c.-418G>A; NM_000594.3)), c.-308G>A (c.-488G>A; NM_000594.3), c.-857C>T (c.-1037C>T; NM_000594.3) and c.-863C>A (c.-1043C>A; NM_000594.3) harboring regions were PCR amplified and sequenced by Sanger sequencing. Allele frequency and genotype distribution in glaucoma cases and controls were compared using chi-square test and genetic association tested using different genetic models. RESULTS Statistically significant genotype and allelic association was observed between glaucoma cases and controls for c.-308G>A and c.-863C>A alterations (p = 0.001, p = 0.001; p = 0.001, p = 0.001 respectively). AA genotype of c.-308G>A conferred ~7 fold increased risk towards glaucoma (OR = 6.82, 95% CI = 2.82-16.53, p = 0.001). c.-863C>A alteration under dominant, recessive and co-dominant genetic models conferred ~2 fold increased risk for glaucoma. However, no association for c.-238G>A and c.-857C>T variants with glaucoma was observed. Further, three haplotypes (GGCA, GACC and GACA) (OR = 0.48, 95% CI = 0.35-0.67, p = 0.001; OR = 0.58, 95% CI = 0.36-0.91, p = 0.019 and OR = 0.16, 95% CI = 0.05-0.51, p = 0.002, respectively) conferred protective role towards glaucoma. CONCLUSIONS Present study is the first to indicate significant association of c.-308G>A and c.-863C>A alterations with glaucoma in cases from north Indian cohort. Also it is the first study from India to analyze the association and interaction of four promoter region alterations (c.-238G>A, c.-308G>A, c.-857C>T and c.-863C>A) in TNF-α resulting in three protective haplotypes.
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Affiliation(s)
- Shruti Passan
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India
| | - Shiwali Goyal
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India
| | - Mohd Akbar Bhat
- Multidisciplinary Research Unit, Government Medical College, Amritsar, Punjab, India
| | - Daljit Singh
- Dr. Daljit Singh Eye Hospital, Amritsar, Punjab, India
| | - Vanita Vanita
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
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Chen L, Huang Z, Liao Y, Yang B, Zhang J. Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis. ACTA ACUST UNITED AC 2019; 52:e7927. [PMID: 30916218 PMCID: PMC6437938 DOI: 10.1590/1414-431x20187927] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 12/10/2018] [Indexed: 02/05/2023]
Abstract
Tumor necrosis factor-alpha (TNF-α) plays an important role in
autoimmune diseases. Previous studies have investigated the association of
TNF-α-238G/A (rs361525) and -308G/A
(rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus
erythematosus (SLE). However, no agreed conclusion had been made. Therefore,
this meta-analysis was conducted to assess the associations of
TNF-α-238G/A and -308G/A polymorphisms
with RA and SLE risk. A systematic search was conducted in commonly used
databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were
included. In the overall population, the TNF-α-238A allele was
observed to be a protective factor for RA (A vs G: OR=0.75,
95%CI=0.57–0.99, P=0.040) and the TNF-α-308A allele was found
to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45–2.19,
P<0.001). However, no evidence of association was found between
TNF-α-238 G/A polymorphism and SLE nor between -308G/A and
RA. In the subgroup analysis, TNF-α-308A allele played a
pathogenic role for RA in Latin Americans (A vs G: OR=1.46,
95%CI=1.15–1.84, P=0.002) and for SLE in Latin Americans (A vs
G: OR=2.12, 95%CI=1.32–3.41, P=0.002) and Europeans (A vs G:
OR=2.03, 95%CI=1.56–2.63, P<0.001), while it played a protective role for RA
in Asians (A vs G: OR=0.54, 95%CI=0.32–0.90, P=0.017). No
significant association was found between TNF-α-308G/A and SLE
susceptibility in Africans and Asians. This meta-analysis demonstrated that
TNF-α-238A was associated with decreased risk of RA rather
than SLE, while -308G/A polymorphism was associated with SLE
rather than RA. Stratification analysis indicated that different ethnicities
would have different risk alleles.
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Affiliation(s)
- Lin Chen
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Zhuochun Huang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yun Liao
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Yang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Junlong Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
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Nejati P, Naeimipour S, Salehi A, Shahbazi M. Association of tumor necrosis factor-alpha gene promoter polymorphism and its mRNA expression level in coronary artery disease. Meta Gene 2018. [DOI: 10.1016/j.mgene.2018.08.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Hassanzad M, Farnia P, Ghanavi J, Parvini F, Saif S, Velayati AA. TNFα -857 C/T and TNFR2 +587 T/G polymorphisms are associated with cystic fibrosis in Iranian patients. Eur J Med Genet 2018; 62:103584. [PMID: 30472484 DOI: 10.1016/j.ejmg.2018.11.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 11/04/2018] [Accepted: 11/22/2018] [Indexed: 02/07/2023]
Abstract
Identification of modifier genes influencing phenotype of cystic fibrosis (CF) patients has become a challenge in CF pathophysiology, prognostic estimations and development of new therapeutic strategies. The aim of this study was to explore the association between four genetic polymorphisms of three modifier genes with CF, by comparing their alleles, genotypes and haplotype frequencies in patients and controls. In this favor, two regulatory polymorphic loci in TNFα promoter (-857C/T, rs1799724 and -238A/G, rs361525) and two functional polymorphic loci in TNFR1 (+36A/G, rs767455) and TNFR2 (+587T/G, rs1061622) were genotyped in 70 patients and 79 controls, using PCR-RFLP. Clinical pulmonary data were also recorded from all studied patients. Results indicated that an association was observed between both T allele and CT/TT genotypes of TNFα (P = 0.0005, OR = 7.06, 95% CI = 3.71-13.45) with CF under dominant model of inheritance. GG genotype of TNFR2 +587 (P = 0.0005, OR = 4.92, 95%CI = 2.34-10.34) was significantly associated with CF using recessive model. Consistently, more severe pulmonary disorder was found for patients carrying either T dominant allele of TNFα -857 or GG genotype of TNFR2 +587 polymorphic sites. Despite an association of A-T and G-T haplotypes with CF, no significant association was found between these haplotypes and clinical parameters of CF. Overall, TNFα -857 T allele and GG genotype of TNFR2 +587 were more frequent in CF patients compared to healthy controls and hence, they showed an association with CF and severe pulmonary phenotype in Iranian patients.
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Affiliation(s)
- Maryam Hassanzad
- Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Poopak Farnia
- Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Jalaledin Ghanavi
- Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farshid Parvini
- Department of Cell and Molecular Biology, Faculty of Science, Semnan University, Semnan, Iran
| | - Shima Saif
- Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Velayati
- Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Yang LT, Liu X, Wu GH, Chen LF. Association between tumor necrosis factor-α -308 Gauss/A polymorphism and risk of silicosis and coal workers pneumoconiosis in Chinese population. Inhal Toxicol 2018; 30:213-217. [PMID: 30257124 DOI: 10.1080/08958378.2018.1494766] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Li-teng Yang
- Department of Respiratory Medicine, Shenzhen Luohu People's Hospital, The Third Affiliatied Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Xin Liu
- Zunyi Medicine-Pharmacology College, Zunyi, Guizhou, China
| | - Gao-hui Wu
- Department of Respiratory Medicine, Shenzhen Luohu People's Hospital, The Third Affiliatied Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Li-fang Chen
- Department of Respiratory Medicine, Shenzhen Luohu People's Hospital, The Third Affiliatied Hospital of Shenzhen University, Shenzhen, Guangdong, China
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Yao YS, Chang WW, Jin YL. Association between TNF-a promoter -308G/A polymorphism and essential hypertension in the Asian population: A meta-analysis. J Renin Angiotensin Aldosterone Syst 2018; 18:1470320317741066. [PMID: 29258412 PMCID: PMC5843847 DOI: 10.1177/1470320317741066] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVE The results of studies on the association between tumor necrosis factor-a -308G/A (TNF-a -308G/A) polymorphism, and susceptibility to essential hypertension are controversial. To derive a more precise estimation, we conducted a meta-analysis of all similar articles. METHODS The summary effect odds ratios and 95% confidence intervals were obtained. Funnel plots and Egger's test were used to estimate publication bias, and heterogeneity was assessed by the chi-square-based Q-test and I2 test. RESULTS Nine studies (with 1437 cases and 1487 controls) were included. In the overall analysis, the combined results showed that there were significant differences in genotype distribution between essential hypertension cases and controls, AA+GA versus GG (OR = 1.53, 95% CI: 1.25-1.88, p < 0.00001). In the stratified analysis by country, we found that essential hypertension cases had a significantly higher frequency of AA+GA versus GG (OR = 1.47, 95% CI: 1.18-1.81, p = 0.0004) than control in the Asian population. CONCLUSIONS This meta-analysis supports previous findings that TNF-a -308G/A polymorphism may increase the risk of essential hypertension, at least in the Asian population.
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Affiliation(s)
- Ying-Shui Yao
- Department of Preventive Medicine, Wannan Medical College, China
| | - Wei-Wei Chang
- Department of Preventive Medicine, Wannan Medical College, China
| | - Yue-Long Jin
- Department of Preventive Medicine, Wannan Medical College, China
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Zhang G, Zhang J, Kuang M, Lin P. The role of TNF alpha polymorphism and expression in susceptibility to nasal polyposis. Immunol Invest 2018; 47:360-371. [PMID: 29388847 DOI: 10.1080/08820139.2018.1433204] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Guimin Zhang
- Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, People’s Republic of China
| | - Jinmei Zhang
- Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, People’s Republic of China
| | - Manbao Kuang
- Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, People’s Republic of China
| | - Peng Lin
- Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, People’s Republic of China
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14
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How gene polymorphisms can influence clinical response and toxicity following R-CHOP therapy in patients with diffuse large B cell lymphoma. Blood Rev 2017; 31:235-249. [DOI: 10.1016/j.blre.2017.02.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Revised: 12/07/2016] [Accepted: 02/03/2017] [Indexed: 12/20/2022]
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15
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Jevtovic-Stoimenov T, Cvetkovic T, Despotovic M, Basic J, Cvetkovic J, Marjanovic G, Pavlovic D. The influence of TNF alpha -308 G/A polymorphism on oxidative stress in patients with chronic lymphocytic leukemia. Leuk Res 2017; 54:66-72. [DOI: 10.1016/j.leukres.2017.01.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 01/09/2017] [Indexed: 01/24/2023]
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16
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Association of G308A and G238A Polymorphisms of the TNF-α Gene with Risk of Coronary Heart Disease: Systematic Review and Meta-analysis. Arch Med Res 2016; 47:557-572. [DOI: 10.1016/j.arcmed.2016.11.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 11/04/2016] [Indexed: 01/06/2023]
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17
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Chonmaitree T, Trujillo R, Jennings K, Alvarez-Fernandez P, Patel JA, Loeffelholz MJ, Nokso-Koivisto J, Matalon R, Pyles RB, Miller AL, McCormick DP. Acute Otitis Media and Other Complications of Viral Respiratory Infection. Pediatrics 2016; 137:peds.2015-3555. [PMID: 27020793 PMCID: PMC4811317 DOI: 10.1542/peds.2015-3555] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/22/2016] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Viral upper and lower respiratory tract infections (URI, LRI) are common in infants. We determined the prevalence of viral URI and its complications, including acute otitis media (AOM) and LRI, and assessed the effect of bacterial-viral interactions, and genetic and environmental risks on AOM development. METHODS Healthy infants were enrolled from near birth and followed to the first episode of AOM up to 12 months of age. Nasopharyngeal specimens were collected at monthly intervals (months 1-6, 9) and during viral URI episodes for bacterial culture and viral polymerase chain reaction studies. Subjects were followed closely for AOM development. RESULTS A total of 367 infants were followed for 286 child-years; 887 URI (305 infants) and 180 AOM episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM incidence by ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and without AOM had 4.7 and 2.3 URI episodes per child-year, respectively (P < .002). Pathogenic bacterial colonization rates by month were significantly higher in infants with AOM (P < .005). Breastfeeding reduced both URI and AOM risks (P < .05). Significant bacterial-viral interactions occurred with Moraxella catarrhalis and a variety of respiratory viruses and altered URI and AOM risks. CONCLUSIONS Almost half of infants experienced AOM by age 1. Important AOM risk factors included frequent viral URI, pathogenic bacterial colonization, and lack of breastfeeding. Bacterial-viral interactions may play a significant role in AOM pathogenesis and deserve further investigation.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Richard B. Pyles
- Departments of Pediatrics, ,Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
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Abutorabi R, Baradaran A, Sadat Mostafavi F, Zarrin Y, Mardanian F. Evaluation of Tumor Necrosis Factor Alpha Polymorphism Frequencies in Endometriosis. INTERNATIONAL JOURNAL OF FERTILITY & STERILITY 2015; 9:329-37. [PMID: 26644856 PMCID: PMC4671386 DOI: 10.22074/ijfs.2015.4548] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 04/12/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), is a pathogenic element for a number of disorders. Previous studies have reported that the -1031 T/C and -238 G/A polymorphisms in the promoter region of the TNF-α gene are important factors in reproductive-related disorders. One of the most common gynecological diseases of women during the reproductive years is endometriosis. This study aims to assess an association between the -1031 T/C, -238 G/A and -308 G/A polymorphisms of the TNF-α gene promoter region to endometriosis. MATERIALS AND METHODS In this case-control study, we enrolled 65 endometriosis patients and 65 matched healthy control women by simple sampling. Polymerase chain reaction (PCR) analysis was used to analyze -1031 T/C, -238 G/A and -308 G/A polymorphisms in the TNF-α gene promoter region. Statistical analysis was performed using the chi-square test. P values less than 0.05 were considered statistically significant. RESULTS We found a strong association between the -1031 T/C polymorphism in the promoter region of the TNF-α gene with endometriosis (P=0.001). There were no significant associations between the -238 G/A (P=0.243) and -308 G/A (P=1) polymorphisms with endometriosis and again endometriosis stages have no association with these polymorphisms. CONCLUSION The -1031 T/C polymorphism and CC genotype can be used as a relevant marker to identify women at risk of developing endometriosis.
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Affiliation(s)
- Roshanak Abutorabi
- Infertility Laboratory, Beheshti Hospital, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azar Baradaran
- Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Sadat Mostafavi
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Yasaman Zarrin
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farahnaz Mardanian
- Department of Obstetrics and Gynecology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Hua XP, Zhang XD, Kwong JS, Zeng XT, Zhang ZJ, Wei WL. Tumor necrosis factor-alpha G-238A polymorphism and coronary artery disease risk: a meta-analysis of 4,222 patients and 4,832 controls. Ther Clin Risk Manag 2015; 11:1429-36. [PMID: 26445542 PMCID: PMC4590639 DOI: 10.2147/tcrm.s87598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The aim of the present study was to investigate the association between tumor necrosis factor-alpha (TNF-α) gene G-238A polymorphism and risk of coronary artery disease (CAD) using a meta-analytical approach. METHODS The PubMed and Embase databases were searched for relevant publications up to January 13, 2015. Four authors (XPH, XDZ, XTZ, and ZJZ) independently selected the studies, extracted, and analyzed the data using the Comprehensive Meta-Analysis software. The sensitivity and subgroups analyses were also performed. Either a fixed effects or a random effects model was used to estimate pooled odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS Finally, ten articles including eleven case-control studies involving 4,222 patients and 4,832 controls were yielded. The results indicated no significant association between G-238A polymorphism and CAD risk (A vs G: OR =1.08, 95% CI =0.89-1.30; AA vs GG: OR =1.15, 95% CI =0.59-2.25; GA vs GG: OR =1.14, 95% CI =0.88-1.48; AA vs [GG + GA]: OR =1.09, 95% CI =0.56-2.14; (GA + AA) vs GG: OR =1.11, 95% CI =0.90-1.38). In the subgroup analyses, similar results were obtained with overall populations. The sensitivity analyses showed that the overall results were robust. No publication bias was detected. CONCLUSION Based on current evidence, we can conclude that TNF-α G-238A polymorphism might not be associated with CAD risk.
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Affiliation(s)
- Xian-Ping Hua
- Department of Cardiology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei Province, People's Republic of China
| | - Xiao-Dong Zhang
- Department of Cardiology and 4th Cadres Ward, General Hospital of Beijing Military Command, Beijing, People's Republic of China
| | - Joey Sw Kwong
- Chinese Evidence-Based Medicine Center and Chinese Cochrane Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xian-Tao Zeng
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China
| | - Zhen-Jian Zhang
- Department of Cardiology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei Province, People's Republic of China
| | - Wan-Lin Wei
- Department of Cardiology and 4th Cadres Ward, General Hospital of Beijing Military Command, Beijing, People's Republic of China
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Moorchung NN, Vasudevan B, Chatterjee M, Grewal RS, Mani NS. A Comprehensive Study of Tumor Necrosis Factor-Alpha Genetic Polymorphisms, its Expression in Skin and Relation to Histopathological Features in Psoriasis. Indian J Dermatol 2015; 60:345-50. [PMID: 26286396 PMCID: PMC4533530 DOI: 10.4103/0019-5154.160477] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Tumor necrosis factor-alpha (TNFα) is an important inflammatory mediator in psoriasis and several genetic polymorphisms of this cytokine have been reported. Majority of studies have focused on the increased G- A polymorphism at the -308 position in psoriasis. There has been no comprehensive study evaluating the genetic polymorphisms, TNFα expression in the skin and histopathology. We are undertaking this study to outline TNFα genetic polymorphisms, its skin expression and histopathological correlation to help determine its role at the genetic and protein level. MATERIALS AND METHODS 112 patients of psoriasis and 243 healthy controls were included in this prospective study. 5 ml of peripheral blood was collected to study the TNFα genetic polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathological analysis of biopsies from the 112 patients were done using visual analogue scale and correlated with the findings. 61 of these cases were analyzed for TNFα expression by immunohistochemistry. The results of study were statistically analyzed using SPSS 13.0 statistical package program. RESULTS A strong association of TNFα -308 G/A polymorphism in psoriasis cases was detected. The A allele of the TNFα -308 G/A polymorphism occurs rarely in the Indian population, however there is an over representation of this allele in psoriatic patients. There was no association seen between TNFα genotype and histopathological severity of psoriasis. CONCLUSION The study emphasized the central role of TNFα in the pathogenesis of psoriasis. TNFα genotyping may be helpful in identifying subjects in whom anti-TNFα therapeutic strategies may be tried.
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Affiliation(s)
- Nikhil N Moorchung
- Department of Pathology, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
| | - Biju Vasudevan
- Department of Dermatology, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
| | - Manas Chatterjee
- Department of Dermatology, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
| | - Rajan Singh Grewal
- Department of Dermatology, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
| | - Narayana S Mani
- Department of Pathology, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
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Song GG, Seo YH, Kim JH, Choi SJ, Ji JD, Lee YH. Association between TNF-α (-308 A/G, -238 A/G, -857 C/T) polymorphisms and responsiveness to TNF-α blockers in spondyloarthropathy, psoriasis and Crohn's disease: a meta-analysis. Pharmacogenomics 2015; 16:1427-37. [DOI: 10.2217/pgs.15.90] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Aim: The aim of this study is to investigate whether TNF-α polymorphisms are associated with the responsiveness to anti-TNF-α therapy in patients with spondyloarthropathy, psoriasis, and Crohn's disease. Methods: We conducted a meta-analysis on the association between the TNF-α polymorphisms and responsiveness of patients. Results: The meta-analysis indicated an association between the TNF-α -308 G allele (OR = 2.005; 95% CI: 1.417–2.838; p = 8.6 × 10-5), TNF-α -238 G allele (OR = 2.196; 95% CI: 1161–4.154; p = 0.016), and TNF-α -857 C allele (OR = 1.779; 95% CI: 1.130–2.802; p = 0.013) and response to TNF-α blockers in Caucasians. Conclusion: Individuals carrying the TNF-α -308 G, -238 G, or -857 C common alleles show better responses to TNF-α blockers than those with minor alleles in Caucasians.
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Affiliation(s)
- Gwan Gyu Song
- Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Young Ho Seo
- Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Jae-Hoon Kim
- Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Sung Jae Choi
- Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Jong Dae Ji
- Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Young Ho Lee
- Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
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Satterfield BC, Wisor JP, Field SA, Schmidt MA, Van Dongen HPA. TNFα G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults. Brain Behav Immun 2015; 47:66-74. [PMID: 25542735 PMCID: PMC4467999 DOI: 10.1016/j.bbi.2014.12.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Revised: 12/02/2014] [Accepted: 12/05/2014] [Indexed: 01/25/2023] Open
Abstract
Cytokines such as TNFα play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFα gene (TNFα G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFα 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFα G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFα in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFα G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation.
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Affiliation(s)
- Brieann C Satterfield
- Sleep and Performance Research Center, Washington State University, Spokane, WA, USA; Graduate Program in Neuroscience, Washington State University, Pullman, WA, USA
| | - Jonathan P Wisor
- Sleep and Performance Research Center, Washington State University, Spokane, WA, USA; College of Medical Sciences, Washington State University, Spokane, WA, USA.
| | - Stephanie A Field
- Internal Medicine Residency, University of Washington, Seattle, WA, USA
| | - Michelle A Schmidt
- Sleep and Performance Research Center, Washington State University, Spokane, WA, USA; College of Medical Sciences, Washington State University, Spokane, WA, USA
| | - Hans P A Van Dongen
- Sleep and Performance Research Center, Washington State University, Spokane, WA, USA; College of Medical Sciences, Washington State University, Spokane, WA, USA
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Meta-analysis of associations between tumor necrosis factor-α polymorphisms and schizophrenia susceptibility. Psychiatry Res 2015; 226:521-2. [PMID: 25752206 DOI: 10.1016/j.psychres.2015.02.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Revised: 02/16/2015] [Accepted: 02/20/2015] [Indexed: 11/20/2022]
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Association between TNF-α promoter −308 A/G polymorphism and Alzheimer’s disease: a meta-analysis. Neurol Sci 2015; 36:825-32. [DOI: 10.1007/s10072-015-2102-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 01/30/2015] [Indexed: 10/24/2022]
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Shattuck EC, Muehlenbein MP. Human sickness behavior: Ultimate and proximate explanations. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2015; 157:1-18. [DOI: 10.1002/ajpa.22698] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 12/27/2014] [Accepted: 12/28/2014] [Indexed: 12/22/2022]
Affiliation(s)
- Eric C. Shattuck
- Evolutionary Physiology and Ecology Laboratory; Department of Anthropology; Indiana University; Bloomington IN
| | - Michael P. Muehlenbein
- Evolutionary Physiology and Ecology Laboratory; Department of Anthropology; Indiana University; Bloomington IN
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Simionescu R, Cherecheanu AP, Voinea L, Sfrenț-Cornățeanu R. TNF-α Gene Polymorphisms and Primary Open Angle Glaucoma in Romanian Population / Polimorfisme ale genei TNF-α în populația română cu glaucom primar cu unghi deschis. REV ROMANA MED LAB 2015. [DOI: 10.1515/rrlm-2015-0004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AbstractPrimary open-angle glaucoma (POAG) represents the most common form of a heterogeneous group of glaucomatous optic neuropathies which are a worldwide cause of irreversible blindness. Immune dysregulation and the genetic background are considered important risk factors. The influence on susceptibility to POAG of single nucleotide polymorphisms (SNPs) of tumor necrosis factor-α (TNF-α) was intensively studied, mostly on Asian population. We investigated the possible association of two TNF-α SNPs (-308G/A and -857C/T) with susceptibility to POAG and its clinical characteristics. A case-control association study of aforementioned TNF-α SNPs was performed on 197 POAG patients (divided into two subgroups: high-tension and normal-tension glaucoma - HTG/ NTG) versus 208 ethnically matched controls. This is the first study performed on Romanian population. No significant differences were found in terms of allelic frequencies, genotype distribution of the studied SNPs, or their haplotypes between POAG and healthy control groups. In the subgroup analysis, TT genotype of TNF-α -857T-allele was found to be associated with higher values of central corneal thickness (CCT) in NTG subgroup (p-value 0.032). In order to confirm the association between -857C/T SNP of TNF-α and CCT in NTG subgroup of POAG patients, additional studies on different populations should be performed.
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TNF-α promoter single nucleotide polymorphisms and haplotypes associate with susceptibility of immune thrombocytopenia in Chinese adults. Hum Immunol 2014; 75:980-5. [PMID: 25158149 DOI: 10.1016/j.humimm.2014.08.197] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Revised: 06/12/2014] [Accepted: 08/14/2014] [Indexed: 10/25/2022]
Abstract
OBJECTIVE Tumor necrosis factor-alpha (TNF-α) participates as a candidate susceptibility factor for immune thrombocytopenia (ITP). This study attempted to investigate the association between five single nucleotide polymorphisms (SNPs) spanning the TNF-α promoter and the susceptibility of primary ITP in Chinese Han adults. METHODS In 215 adult primary ITP patients and 206 healthy controls, SNPs were detected by PCR-RFLP and PCR-SSP. The χ(2) test or fisher's exact test was used to compare frequencies of genotypes and alleles between patients and controls. Haplotypes were analyzed with the SHEsis online program. TNF-α, IFN-γ and Galectin-9 mRNA of 35 newly diagnosed adult ITP patients and 35 healthy controls were detected by qRT-PCR. RESULTS The haplotype GGC (-238G/-308G/-857C) of TNF-α promoter was significantly associated with a decreased susceptibility of primary ITP, especially in males. The relative levels of mRNA expression of TNF-α, IFN-γ and Gal-9 in adult active primary ITP patients was significantly up-regulated compared with patients in remission and controls. CONCLUSIONS This study represented the first report that the haplotype GGC of TNF-α was differentially associated with the susceptibility of primary ITP in Chinese Han adults. The up-regulation of TNF-α, IFN-γ and Galectin-9 was significantly correlated with active primary ITP in adult patients.
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Chen S, Wang Q, Wu Z, Wu Q, Li P, Li Y, Li J, Deng C, Wu C, Gao L, Zhang F, Li Y. Associations between TNF-α-308A/G polymorphism and susceptibility with dermatomyositis: a meta-analysis. PLoS One 2014; 9:e102841. [PMID: 25101759 PMCID: PMC4125139 DOI: 10.1371/journal.pone.0102841] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 06/23/2014] [Indexed: 11/19/2022] Open
Abstract
Background Some surveys had inspected the effects of the tumor necrosis factor-α (TNF-α)-308A/G polymorphism on susceptibility to dermatomyositis (DM), and showed mixed results. To briefly review these consequences, a comprehensive meta-analysis was carried out to estimate the relationship between them much more accurately. Methods Relevant documents dated to February 2014 were acquired from the PUBMED, MEDLINE, and EMBASE databases. The number of the genotypes and/or alleles for the TNF-α-308A/G in the DM and control subjects was extracted and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were used to calculate the risk of DM with TNF-α-308A/G. Stratified analysis based on ethnicity and control population source was also performed. Results 555 patients with DM and 1005 controls from eight published investigations were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the TNF-α-308A allele were 2.041 (95% CIs 1.528–2.725, P<0.0001) in DM. Stratification by ethnicity indicated the TNF-α-308A allele polymorphism was found to be significantly associated with DM in Europeans (OR = 1.977, 95% CI 1.413–2.765, P<0.0001). The only study conducted on TNF-α-308A/G polymorphism in Asians could not be used in ethnicity-stratified meta-analysis. Meta-analysis of the AA+AG vs. GG (dominant model) and AA vs. GG (additive model) of this polymorphism revealed a significant association with DM in overall populations and Europeans. Conclusions Our meta-analysis demonstrated that the TNF-α-308A/G polymorphism in the TNF gene might contribute to DM susceptibility, especially in European population. However, further studies with large sample sizes and among different ethnicity populations should be required to verify the association.
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Affiliation(s)
- Si Chen
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ziyan Wu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Qingjun Wu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ping Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yuan Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jing Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Chuiwen Deng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Chanyuan Wu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Lei Gao
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Fengchun Zhang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yongzhe Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
- * E-mail:
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Zubor P, Dokus K, Zigo I, Skerenova M, Pullmann R, Danko J. TNF α G308A gene polymorphism has an impact on renal function, microvascular permeability, organ involvement and severity of preeclampsia. Gynecol Obstet Invest 2014; 78:150-61. [PMID: 25059926 DOI: 10.1159/000364865] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 05/27/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance. The role of tumor necrosis factor-α (TNF-α), a cytokine involved in inflammation processes, has been widely investigated in obstetric disorders. The aims of the present study were to investigate the effect of TNF-α gene G308A (rs1800629) polymorphism on disease risk, renal function, microvascular permeability, endothelial cell dysfunction and organ involvement in women with PE. METHODS Initially, 102 3rd-trimester pregnant women (preeclamptic cases and healthy controls) with singleton pregnancy were invited for participation, of which 76 were genotyped for TNF-α G308A polymorphism and evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), fibronectin and TNF-α, which were tested for correlations with the profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to test the association between the TNF-α polymorphism and PE risk. For continuous variables, we applied Student's t test and, for categorical variables, the Pearson χ(2) or Fisher's exact test. The two-way ANOVA test with Bonferroni correction was used in multivariate analyses. RESULTS The A allele was more frequent in cases than controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal serum levels of TNF-α, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/ml, 1,243 ± 671 ng/ml, 0.308 ± 0.231 g/l, respectively) compared to controls (301.1 ± 156.1 pg/ml, 651 ± 250 ng/ml, 0.218 ± 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031, respectively), and these levels showed an increasing trend with the mutant allele genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p < 0.01), respectively). The adverse effect of rs1800629 allele A on renal function was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. CONCLUSION This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.
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Affiliation(s)
- Pavol Zubor
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic
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TNF-308 G/A polymorphism and risk of acne vulgaris: a meta-analysis. PLoS One 2014; 9:e87806. [PMID: 24498378 PMCID: PMC3912133 DOI: 10.1371/journal.pone.0087806] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2013] [Accepted: 12/30/2013] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The -308 G/A polymorphism in the tumor necrosis factor (TNF) gene has been implicated in the risk of acne vulgaris, but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -308 G/A polymorphism and acne vulgaris risk. METHODS We searched in Pubmed, Embase, Web of Science and CNKI for studies evaluating the association between the -308 G/A gene polymorphism and acne vulgaris risk. Data were extracted and statistical analysis was performed using STATA 12.0 software. RESULTS A total of five publications involving 1553 subjects (728 acne vulgaris cases and 825 controls) were included in this meta-analysis. Combined analysis revealed a significant association between this polymorphism and acne vulgaris risk under recessive model (OR = 2.73, 95% CI: 1.37-5.44, p = 0.004 for AA vs. AG + GG). Subgroup analysis by ethnicity showed that the acne vulgaris risk associated with the -308 G/A gene polymorphism was significantly elevated among Caucasians under recessive model (OR = 2.34, 95% CI: 1.13-4.86, p = 0.023). CONCLUSION This meta-analysis suggests that the -308 G/A polymorphism in the TNF gene contributes to acne vulgaris risk, especially in Caucasian populations. Further studies among different ethnicity populations are needed to validate these findings.
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Nagy ZB, Csanád M, Tóth K, Börzsönyi B, Demendi C, Rigó J, Joó JG. Current concepts in the genetic diagnostics of rheumatoid arthritis. Expert Rev Mol Diagn 2014; 10:603-18. [PMID: 20629510 DOI: 10.1586/erm.10.36] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Zsolt B Nagy
- Nagy Gene Diagnostics and Research LTD, 1054 Budapest, Petofi tér 3, Hungary
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Song GG, Bae SC, Kim JH, Lee YH. Association between TNF-α promoter –308 A/G polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatol Int 2013; 34:465-71. [DOI: 10.1007/s00296-013-2919-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 11/28/2013] [Indexed: 12/23/2022]
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Song GG, Kim JH, Lee YH. Associations between TNF-α −308 A/G and lymphotoxin-α +252 A/G polymorphisms and susceptibility to sarcoidosis: a meta-analysis. Mol Biol Rep 2013; 41:259-67. [DOI: 10.1007/s11033-013-2859-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Accepted: 10/31/2013] [Indexed: 11/30/2022]
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Elhawary NA, Tayeb MT, Abdel-Ghafar S, Rashad M, Alkhotani AA. TNF-238 polymorphism may predict bronchopulmonary dysplasia among preterm infants in the Egyptian population. Pediatr Pulmonol 2013; 48:699-706. [PMID: 23359489 DOI: 10.1002/ppul.22748] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2012] [Accepted: 11/12/2012] [Indexed: 02/05/2023]
Abstract
UNLABELLED Bronchopulmonary dysplasia (BPD) remains as a major and increasing burden in Egypt. RATIONALE To determine whether alleles of TNFα-238G > A affect the risk of BPD or the severity of BPD in preterm infants in Egypt. STUDY DESIGN We prospectively genotyped 220 premature neonates (birth weight <1,500 g and gestational age 26-32 weeks) for the -238 polymorphism, and assessed the clinical risk factors for BPD in our study populations. Infants with BPD were mechanically ventilated. RESULTS Infants who developed BPD (n = 120) had a younger gestational age (31.0 ± 2.1 weeks vs. 34.3 ± 1.5 weeks) and lower birth weight (1,490 ± 360 g vs. 1,880 ± 520 g) than infants who did not develop BPD (n = 100). Results of antenatal steroid supplementation, surfactant therapy, or sepsis might affect the genetic modulation of BPD. The -238G > A polymorphism was associated with a twofold risk of BPD (OR = 2.86; 95% confidence interval, 1.35-3.83). Despite the dominance of the G allele in the Egyptian population, the -238A allele was more common among infants with BPD (23%) than among infants without BPD (15%). The A allele occurred less often in infants with mild BPD (9%) than in infants with severe (39%) or moderate (52%). The AA genotype occurred in 15% of cases but in none of the controls. CONCLUSION The TNFα -238G > A polymorphism-particularly the presence of an A allele-should be evaluated as a biomarker to predict the clinical outcome of preterm infants with BPD in Egypt. Even the presence of one copy of this mutant allele appears to be sufficient to influence the severity of disease.
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Affiliation(s)
- Nasser A Elhawary
- Faculty of Medicine, Department of Medical Genetics, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia.
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Association between tumor necrosis factor-α promoter −308 A/G, −238 A/G, interleukin-6 −174 G/C and −572 G/C polymorphisms and periodontal disease: a meta-analysis. Mol Biol Rep 2013; 40:5191-203. [DOI: 10.1007/s11033-013-2621-4] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Accepted: 04/30/2013] [Indexed: 10/26/2022]
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Titmarsh CJ, Moscovis SM, Hall S, Tzanakaki G, Kesanopoulos K, Xirogianni A, Scott RJ, Blackwell CC. Comparison of cytokine gene polymorphisms among Greek patients with invasive meningococcal disease or viral meningitis. J Med Microbiol 2013; 62:694-700. [PMID: 23378564 DOI: 10.1099/jmm.0.058073-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
High levels of pro-inflammatory cytokines are implicated in the severity of invasive meningococcal disease (IMD) and viral meningitis (VM). This study compared single-nucleotide polymorphisms (SNPs) in pro- and anti-inflammatory cytokine genes among patients with VM or IMD. Patient DNA samples were prepared by the National Meningitis Reference Laboratory in Athens: n=98 for IMD and n=53 for VM. The results for both patient groups were compared with data published for healthy Greek control data. Real-time PCR was used to assess the interleukin (IL) gene SNPs IL6 G-174C, IL1B C-511T, IL1RN T+2018C, IL10 G-1082A and IL8 A-251T and the tumour necrosis factor α (TNF-α) SNP TNFA G-308A. Differences were compared by Fisher's exact test. The genotype for high IL-6 responses was predominant among IMD (51%, P=0.0008) and VM (74.5%, P<0.0001) patients compared with the controls (31%). The genotype associated with high TNF-α responses was 5% among controls and lower for IMD (1.1%, P=0.0014) and VM (0%, P=0.052). There was no difference for IL-8 SNPs between controls and IMD (P=0.162), but the difference was significant for VM (P=0.0025). IL-6 (P=0.024) and IL-8 (P=0.00004) SNPs differed between IMD and VM. Reports on associations between IL-8 SNPs and cytokine responses differ. Because of its role in neutrophil attraction, differences in frequencies of the IL-8 SNP for IMD and VM require further investigation.
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Affiliation(s)
| | | | - Sharron Hall
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- University of Newcastle, Newcastle, NSW, Australia
| | - Georgina Tzanakaki
- National Meningitis Reference Laboratory, National School of Public Health, Athens, Greece
| | | | - Athanasia Xirogianni
- National Meningitis Reference Laboratory, National School of Public Health, Athens, Greece
| | - Rodney J Scott
- Hunter Area Pathology Service Genetics, University of Newcastle, Newcastle, NSW, Australia
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- University of Newcastle, Newcastle, NSW, Australia
| | - C Caroline Blackwell
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- University of Newcastle, Newcastle, NSW, Australia
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Hsu J, Avila PC, Kern RC, Hayes MG, Schleimer RP, Pinto JM. Genetics of chronic rhinosinusitis: state of the field and directions forward. J Allergy Clin Immunol 2013; 131:977-93, 993.e1-5. [PMID: 23540616 PMCID: PMC3715963 DOI: 10.1016/j.jaci.2013.01.028] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Revised: 01/10/2013] [Accepted: 01/11/2013] [Indexed: 01/15/2023]
Abstract
The cause of chronic rhinosinusitis (CRS) remains unclear. Study of the genetic susceptibility to CRS might be a valuable strategy to understand the pathogenesis of this burdensome disorder. The purpose of this review is to critically evaluate the current literature regarding the genetics of CRS in a comprehensive fashion. The most promising findings from candidate gene studies include the cystic fibrosis transmembrane conductance regulator gene (CFTR), as well as genes involved in antigen presentation, innate and adaptive immune responses, tissue remodeling, and arachidonic acid metabolism. We also review the few hypothesis-independent genetic studies of CRS (ie, linkage analysis and pooling-based genome-wide association studies). Interpretation of the current literature is limited by challenges with study design, sparse replication, few functional correlates of associated polymorphisms, and inadequate examination of linkage disequilibrium or expression quantitative trait loci for reported associations. Given the relationship of CRS to other airway disorders with well-characterized genetic components (eg, asthma), study of the genetics of CRS deserves increased attention and investment, including the organization of large, detailed, and collaborative studies to advance knowledge of the mechanisms that underlie this disorder.
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Affiliation(s)
- Joy Hsu
- Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60637, USA
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The applied basic research of systemic lupus erythematosus based on the biological omics. Genes Immun 2013; 14:133-46. [PMID: 23446742 DOI: 10.1038/gene.2013.3] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies directed against nuclear self-antigens and circulating immune complexes. This results in damages to various organs or systems, including skin, joints, kidneys and the central nervous system. Clinical manifestations of SLE could be diverse, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures and arthritis. The complicated pathogenesis and varied clinical symptoms of SLE pose great challenges in the diagnosis and monitoring of this disease. Unfortunately, the etiological factors and pathogenesis of SLE are still not completely understood. It is noteworthy that recent advances in our understanding of the biological omics and emerging technologies have been providing new tools in the analyses of SLE, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics and so on. In this article, we summarize our current knowledge in this field for a better understanding of the pathogenesis, diagnosis and treatment for SLE.
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Shmarina G, Pukhalsky A, Petrova N, Zakharova E, Avakian L, Kapranov N, Alioshkin V. TNF gene polymorphisms in cystic fibrosis patients: contribution to the disease progression. J Transl Med 2013; 11:19. [PMID: 23343370 PMCID: PMC3565881 DOI: 10.1186/1479-5876-11-19] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Accepted: 01/18/2013] [Indexed: 02/06/2023] Open
Abstract
Background It is well known that the disease progression in cystic fibrosis (CF) patients may be diverse in subjects with identical mutation in CFTR gene. It is quite possible that such heterogeneity is associated with TNF-α and/or LT-α gene polymorphisms since their products play a key role in inflammation. The aim of the study was to investigate the possible roles of TNF gene polymorphisms in CF disease phenotype and progression. Methods 198 CF patients and 130 control subjects were genotyped for both TNF-α–308GA and LT-α + 252AG polymorphisms. Results The carriers of the TNF-α–308A allele more frequently had asthma as compared to patients homozygous for the TNF-α–308 G allele. In 9 of 108 (8.3%) of LTα + 252AA carriers, tuberculosis infection has been documented, whereas there was no case of tuberculosis among patients, either homozygous or heterozygous for LTα +252 G alleles (p = 0.01). We never observed virus hepatitis among LTα + 252GA carriers. The genotypes TNF-α–308GG – LT-α + 252AA and TNF-α–308GA – LT-α + 252AG were unfavorable with regard to liver disease development (both p < 0.05). It was also shown that neutrophil elastase activity was higher in sputum specimens from high TNF producers with genotypes TNF-α–308GA or LT-α + 252GG. In addition the carriers of such genotypes demonstrated a higher risk of osteoporosis development (p values were 0.011 and 0.017, respectively). Conclusions The carriers of genotypes, which are associated with higher TNF-α production, demonstrated increased frequency of asthma, higher levels of neutrophil elastase, and decrease of bone density. On the contrary, the carriers of genotypes associated with low TNF-α production showed a higher frequency of tuberculosis infection.
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Affiliation(s)
- Galina Shmarina
- Department of Cystic Fibrosis, Research Centre for Medical Genetics, 1 Moskvorechie Street, Moscow 115478, Russia
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Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients. Cytokine 2013; 61:218-22. [DOI: 10.1016/j.cyto.2012.09.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2012] [Revised: 09/24/2012] [Accepted: 09/26/2012] [Indexed: 01/11/2023]
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Eğin Y, Elsayed S, Sakr M, Akar N. TNF-α-308 G/A Polymorphism in Egyptian Budd-Chiari Syndrome Patients. Turk J Haematol 2012; 29:420-1. [PMID: 24385733 PMCID: PMC3781630 DOI: 10.5505/tjh.2012.71473] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Accepted: 09/19/2012] [Indexed: 11/21/2022] Open
Affiliation(s)
- Yonca Eğin
- Ankara University, Department of Pediatric Genetics, Ankara, Turkey
| | - Solaf Elsayed
- Ain Shams University, Pediatrics Department, Genetics Unit, Cairo, Egypt
| | | | - Nejat Akar
- TOBB Economy and Technology University Hospital, Ankara, Turkey
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Muñoz SA, Aranda F, Allievi A, Orden AO, Perés Wingeyer S, Trobo R, Alvarez A, Eimon A, Barreira JC, Schneeberger E, Dal Pra F, Sarano J, Hofman J, Chamorro J, de Larrañaga G. 4G/5G plasminogen activator inhibitor-1 and −308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis. Clin Exp Med 2012; 14:83-9. [DOI: 10.1007/s10238-012-0221-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Accepted: 10/30/2012] [Indexed: 11/28/2022]
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Tumor necrosis factor gene variation predicts hippocampus volume in healthy individuals. Biol Psychiatry 2012; 72:655-62. [PMID: 22554453 DOI: 10.1016/j.biopsych.2012.04.002] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 03/20/2012] [Accepted: 04/05/2012] [Indexed: 12/25/2022]
Abstract
BACKGROUND Cytokines such as tumor necrosis factor (TNF) α have been implicated in neurodegeneration relevant to various neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative properties of cytokine genes on brain function and on hippocampus (HC) function in particular. In this study we investigate the neurodegenerative role of TNF polymorphisms on brain morphology in healthy individuals. METHODS Voxel-based morphometry was used in a large sample of healthy individuals (n = 303) to analyze the associations between genetic variants of TNF (rs1800629; rs361525) and brain morphology (gray matter concentration). RESULTS In a region of interest analysis of the HC, for rs1800629, we observed a strong genotype effect on bilateral HC gray matter concentration. Carriers of one or two A-alleles had significantly smaller volumes compared with GG-homozygotes. For rs361525, a similar effect was observed at almost the same location, with the A-allele resulting in smaller HC volumes compared with GG homozygotes. CONCLUSIONS The findings suggest a neurodegenerative role of the A-alleles of the TNF single nucleotide polymorphisms rs1800629 (-308G/A) and rs361525 (-238G/A) on hippocampal volumes in healthy individuals. Future imaging studies on the role of these single nucleotide polymorphisms in psychiatric populations of diseases with neurodegenerative components are warranted.
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Chu H, Yang J, Mi S, Bhuyan SS, Li J, Zhong L, Liu S, Tao Z, Li J, Chen H. Tumor necrosis factor-alpha G-308 A polymorphism and risk of coronary heart disease and myocardial infarction: A case-control study and meta-analysis. J Cardiovasc Dis Res 2012; 3:84-90. [PMID: 22629023 PMCID: PMC3354475 DOI: 10.4103/0975-3583.95359] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Objectives: The tumor necrosis factor-alpha (TNF-α) gene may play an important role in coronary heart disease (CHD) and myocardial infarction (MI) risk. Recently, controversial results regarding the association of the G-308 A (rs1800629)polymorphism of the TNF-α gene with CHD/MI have been reported. We herein examine a possible association between the G-308 A (rs1800629)polymorphism of the TNF-α gene and CHD/MI in a sample of the Chinese Han population. Materials and Methods: We determined the genotypes of TNF-α G-308 A (rs1800629) in 535 unrelated Chinese patients with CHD, 420 patients with MI, and 1020 coronary artery disease-free controls. Additionally, a meta-analysis of all previous studies on the TNF-α G-308 A polymorphism and the risk of CHD and MI was performed. Results: AA genotypes in the G-308 A (rs1800629)polymorphism of the TNF-α gene did not occur more frequently in CHD/MI patients than in controls; odds ratios (95% confidence intervals) were 1.743 (0.325 to 1.423) for CHD and 1.731 (0.442 to 1.526) for MI, after adjusting for conventional risk factors. Further stratification for age, gender, and other cardiovascular risk factors did not alter the prior negative findings. Pooled meta-analysis of 23 studies also found no statistically significant associations between the TNF-α polymorphism and CHD/MI risk in the genetic additive, dominant, and recessive models. Subgroup analyses showed no association between the TNF-α polymorphism and CHD/MI in Asian and Caucasian populations. Conclusion: Our study showed no association between the G-308 A (rs1800629) polymorphism of the TNF-α gene (presence of A allele) and CHD/MI in the Chinese Han population. There was no evidence of a difference in risk effects of rs1800629 between Caucasians and Asians.
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Affiliation(s)
- Hongxia Chu
- Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Zeng Z, Duan Z, Zhang T, Wang S, Li G, Gao J, Ye D, Xu S, Xu J, Zhang L, Pan F. Association between tumor necrosis factor-α (TNF-α) promoter -308 G/A and response to TNF-α blockers in rheumatoid arthritis: a meta-analysis. Mod Rheumatol 2012; 23:489-95. [PMID: 22760475 DOI: 10.1007/s10165-012-0699-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Accepted: 06/06/2012] [Indexed: 10/28/2022]
Abstract
OBJECTIVES Tumor necrosis factor (TNF)-α promoter -308G/A polymorphism has been shown to be associated with high TNF-α production and poor response to anti-TNF-α treatment. However, not all patients show a good response to TNF-α antagonists, so this association remains controversial. This study was designed to investigate whether TNF-α promoter -308 G/A polymorphism is associated with responsiveness to anti-TNF therapy in rheumatoid arthritis (RA) patients. The 28-joint count Disease Activity Score (DAS) 28 or the American College of Rheumatology (ACR) improvement criteria 20 were used to measure patient response. METHODS A meta-analysis was performed. Pooled ORs and 95 % CIs were calculated by both dominant and recessive genetic models. RESULTS Fifteen studies with a total of 2127 patients were included in this meta-analysis. The results showed that patients with the G allele responded better to the treatment (OR = 1.87, 95 % CI 1.26-2.79). A subanalysis showed similar results. CONCLUSIONS Based on the results of this meta-analysis, RA patients with the TNF-α promoter -308 G allele respond better to TNF-α antagonist treatment, suggesting that this allele plays a major role in anti-TNF-alpha treatment response.
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Affiliation(s)
- Zhen Zeng
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China
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Radouane A, Oudghiri M, Chakib A, Bennani S, Touitou I, Barat-Houari M. SNPs in the TNF- gene promoter associated with Behcet's disease in Moroccan patients. Rheumatology (Oxford) 2012; 51:1595-9. [DOI: 10.1093/rheumatology/kes141] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Lee YH, Bae SC, Song GG. TNF promoter -308 A/G and -238 A/G polymorphisms and juvenile idiopathic arthritis: a meta-analysis. Mol Biol Rep 2012; 39:8497-503. [PMID: 22696185 DOI: 10.1007/s11033-012-1704-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Accepted: 06/06/2012] [Indexed: 11/29/2022]
Abstract
The aim of this study was to determine whether the tumor necrosis factor (TNF) promoter polymorphisms confer susceptibility to juvenile idiopathic arthritis (JIA). A meta-analysis was conducted on the A allele of the TNF -308 A/G and -238 A/G polymorphisms. The nine comparison studies including 1,132 JIA patients and 1,663 controls were included in the meta-analysis and consisted of 7 European, 1 Mexican, and 1 Turkish population. No association was found between JIA and the TNF -308 A allele and the TNF -238 A allele (odds ratio [OR] = 1.211, 95 % confidence interval [CI] = 0.917-1.598, P = 0.177; OR = 1.135, 95 % CI = 0.603-1.861, P = 0.615, respectively). Stratification by ethnicity did not show the association of the TNF -308 and -238 polymorphisms with JIA in Europeans. Mexicans were found to have lower prevalences of A alleles (2.9, 4.1 %) of the TNF -308 A/G and -238 A/G polymorphisms than any other population studied, and the Turkish population the highest (31.2, 26.9 %). This meta-analysis shows no association between the A alleles of the TNF -308 A/G or -238 A/G polymorphisms and JIA in Europeans, but that the prevalences of these alleles are ethnicity dependent.
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Affiliation(s)
- Young Ho Lee
- Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea.
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Ferdinands JM, Denison AM, Dowling NF, Jost HA, Gwinn ML, Liu L, Zaki SR, Shay DK. A pilot study of host genetic variants associated with influenza-associated deaths among children and young adults. Emerg Infect Dis 2012; 17:2294-302. [PMID: 22172537 PMCID: PMC3311214 DOI: 10.3201/eid1712.111002] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Low-producing MBL2 genotypes may have increased risk for MRSA co-infection. We compared the prevalence of 8 polymorphisms in the tumor necrosis factor and mannose-binding lectin genes among 105 children and young adults with fatal influenza with US population estimates and determined in subanalyses whether these polymorphisms were associated with sudden death and bacterial co-infection among persons with fatal influenza. No differences were observed in genotype prevalence or minor allele frequencies between persons with fatal influenza and the reference sample. Fatal cases with low-producing MBL2 genotypes had a 7-fold increased risk for invasive methicillin-resistant Staphylococcus aureus (MRSA) co-infection compared with fatal cases with high- and intermediate-producing MBL2 genotypes (odds ratio 7.1, 95% confidence interval 1.6–32.1). Limited analysis of 2 genes important to the innate immune response found no association between genetic variants and fatal influenza infection. Among children and young adults who died of influenza, low-producing MBL2 genotypes may have increased risk for MRSA co-infection.
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