Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P=6.79x10(-10); odds ratio, 3.47) and was possibly linked to an effect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P=3.02x10(-19)) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.
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PMID:Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). 1911 49

A genome-wide association study of people with incident human immunodeficiency virus (HIV) infection selected from nine different cohorts identified allelic polymorphisms, which associated with either viral set point (HCP5 and 5' HLA-C) or with HIV disease progression (RNF39 and ZNRD1). To determine the influence of these polymorphisms on host control of HIV, we carried out a population-based association study. The analysis revealed complete linkage disequilibrium between HCP5 and HLA-B*5701/HLA-Cw*06, a modest effect of 5' HLA-C on viral set point in the absence of HLA-B*5701, and no influence of the RNF39 /ZNRD1 extended haplotype on HIV disease progression. No correlation was found between the infection status and any of these genetic variants (P>0.1, Fisher's exact test). These findings suggest a pattern of strong linkage disequilibrium consistent with an HLA-B/-C haplotype block, making identification of a causal variant difficult, and underscore the importance of validating polymorphisms in putative determinants for host control by association analysis of independent populations.
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PMID:The HLA-B/-C haplotype block contains major determinants for host control of HIV. 1969 88

Patients demonstrate notable variations in disease progression following human immunodeficiency virus (HIV) infection. We aimed to identify ZNRD1 and RNF39 genetic variants linked to AIDS progression. We conducted a genetic association study in HIV-1-infected Han Chinese patients residing in Taiwan. The clinical characteristics of 143 HIV-1-infected patients were measured, and patients were split into 2 groups: AIDS progression and AIDS non-progression. Genotyping of ZNRD1 and RNF39 was performed in all participants. We found that patients in the AIDS progression group had higher HIV-1 viral loads and lower CD4 cell counts than did patients in the AIDS non-progression group. The frequency of the AA genotype of ZNRD1 (rs16896970) was lower in the AIDS progression group than in the AIDS non-progression group. Patients with AA genotypes had lower levels of HIV-1 viral loads and higher levels of CD4 cell counts than did patients with AG+GG genotypes. AIDS progression in patients with the AA group is significantly different from that in patients with the AG and GG groups by using Kaplan-Meier survival analysis. The hazard ratio for progression was lower in the AA group than in the AG and GG groups. We identified a SNP that contributes to AIDS progression in HIV-1-infected patients in this population. This SNP had a significant protective influence on AIDS progression, and polymorphisms of the ZNRD1 gene may play a role in the pathogenesis of HIV-1 infection.
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PMID:Variants in ZNRD1 gene predict HIV-1/AIDS disease progression in a Han Chinese population in Taiwan. 2387 30