Dataset Information

Structure of tumor necrosis factor-alpha haploblocks in European populations.

ABSTRACT: DNA variants in the tumor necrosis factor-? (TNF) and linked lymphotoxin-? genes, and specific alleles of the highly polymorphic human leukocyte antigen B (HLA-B) gene have been implicated in a plethora of immune and infectious diseases. However, the tight linkage disequilibrium characterizing the central region of the human major histocompatibility complex (MHC) containing these gene loci has made difficult the unequivocal interpretation of genetic association data. To alleviate these difficulties and facilitate the design of more focused follow-up studies, we investigated the structure and distribution of HLA-B-specific MHC haplotypes reconstructed in a European population from unphased genotypes at a set of 25 single nucleotide polymorphism sites spanning a 66-kilobase long region across TNF. Consistent with the published data, we found limited genetic diversity across the so-called TNF block, with the emergence of seven common MHC haplotypes, termed TNF block super-haplotypes. We also found that the ancestral haplotype 8.1 shares a TNF block haplotype with HLA-B*4402. HLA-B*5701, a known protective allele in HIV-1 pathogenesis, occurred in a unique TNF block haplotype.

SUBMITTER: Merino AM

PROVIDER: S-EPMC3985396 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structure of tumor necrosis factor-alpha haploblocks in European populations.

Merino Aimee M AM Zhang Kui K Kaslow Richard A RA Aissani Brahim B

Immunogenetics 20130412 7

DNA variants in the tumor necrosis factor-α (TNF) and linked lymphotoxin-α genes, and specific alleles of the highly polymorphic human leukocyte antigen B (HLA-B) gene have been implicated in a plethora of immune and infectious diseases. However, the tight linkage disequilibrium characterizing the central region of the human major histocompatibility complex (MHC) containing these gene loci has made difficult the unequivocal interpretation of genetic association data. To alleviate these difficult ...[more]

PMID: 23579626

Similar Datasets

Project description:PURPOSE: This meta-analysis was performed to clarify the association between tumor necrosis factor alpha (TNF-?) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-? level in aqueous humor (AH) and the risks of glaucoma. METHODS: A computerized literature search was performed for the relevant available studies from three databases including PubMed, ISI Web of Science, and Embase. The fixed or random effect model was selected based on the heterogeneity test using the Q test and the I(2) statistic. The associations between TNF-? gene polymorphisms and OAG risks were estimated by calculating pooled odds ratios (ORs) and the 95% confidence interval (CI), while a pooled standardized mean difference with 95% CI was used for the comparison of TNF-? levels in AH between patients with OAG and controls. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS: A total of 14 (1,182 cases and 3,003 controls), five (808 cases and 1,039 controls), three (645 cases and 666 controls), and three studies (404 cases and 625 controls) were finally included in the analyses for the associations between TNF-? -308G/A, -857C/T, -863C/A, and -238G/A polymorphisms and the risks of OAG, respectively. The combined results showed that the TNF-? -308G/A gene polymorphism was significantly associated with risks of high-tension glaucoma (A versus G: OR=1.660, 95% CI=1.033-2.667; AA/AG versus GG: OR=1.713, 95% CI=1.10-2.651), but not with normal tension glaucoma or exfoliation glaucoma. Ethnicity-stratified analysis revealed that a significant association also existed in Asians (A versus G: OR=1.947, 95% CI=1.097-3.456; AA/AG versus GG: OR=1.949, 95% CI=1.140-3.332). None of the other polymorphisms was significantly associated with OAG risks. Furthermore, the pooled results of six studies showed that the TNF-? levels in the AH of patients with OAG was higher than that of the control subjects (standardized mean difference=0.517, 95% CI=0.207-0.826, p=0.001). Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. CONCLUSIONS: This meta-analysis suggests that patients with OAG may have higher TNF-? levels compared with the control subjects, and the TNF-? -308G/A polymorphism is significantly associated with the risks of high-tension glaucoma. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.

Dataset Information

Structure of tumor necrosis factor-alpha haploblocks in European populations.

Publications

Structure of tumor necrosis factor-alpha haploblocks in European populations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure