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Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection.

ABSTRACT: High-throughput genome-wide techniques have facilitated the identification of previously unknown host proteins involved in cellular human immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used small interfering RNA technology to silence each gene in the human genome to determine the importance of each in HIV infection. Genes conferring a significant effect were termed HIV-dependency factors (HDFs).We assembled high-density panels of 6380 single-nucleotide polymorphisms (SNPs) in 278 HDF genes and tested for genotype associations with HIV infection and AIDS progression in 1633 individuals from clinical AIDS cohorts.After statistical correction for multiple tests, significant associations with HIV acquisition were found for SNPs in 2 genes, NCOR2 and IDH1. Weaker associations with AIDS progression were revealed for SNPs within the TM9SF2 and EGFR genes.This study independently verifies the influence of NCOR2 and IDH1 on HIV transmission, and its findings suggest that variation in these genes affects susceptibility to HIV infection in exposed individuals.

SUBMITTER: Chinn LW

PROVIDER: S-EPMC3107555 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection.

Chinn Leslie W LW Tang Minzhong M Kessing Bailey D BD Lautenberger James A JA Troyer Jennifer L JL Malasky Michael J MJ McIntosh Carl C Kirk Gregory D GD Wolinsky Steven M SM Buchbinder Susan P SP Gomperts Edward D ED Goedert James J JJ O'Brien Stephen J SJ

The Journal of infectious diseases 20101201 12

<h4>Background</h4>High-throughput genome-wide techniques have facilitated the identification of previously unknown host proteins involved in cellular human immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used small interfering RNA technology to silence each gene in the human genome to determine the importance of each in HIV infection. Genes conferring a significant effect were termed HIV-dependency factors (HDFs).<h4>Methods</h4>We assembled high-density panels of 6 ...[more]

PMID: 21083371

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Project description:BACKGROUND: The transcription factor Nrf2, encoded by the NFE2L2 gene, is an important regulator of the cellular protection against oxidative stress. Parkinson's disease is a neurodegenerative disease highly associated with oxidative stress. In a previously published study, we reported associations of NFE2L2 haplotypes with risk and age at onset of idiopathic Parkinson's disease in a Swedish discovery material and a Polish replication material. Here, we have extended the replication study and performed meta-analyses including the Polish material and four new independent European patient-control materials. Furthermore, all SNPs included in the haplotype windows were investigated individually for associations with Parkinson's disease in meta-analyses including all six materials. METHODS: Totally 1038 patients and 1600 control subjects were studied. Based on previous NFE2L2 haplotype associations with Parkinson's disease, five NFE2L2 tag SNPs were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. The impact of individual SNPs and haplotypes on risk and age at onset of Parkinson's disease were investigated in each material individually and in meta-analyses of the obtained results. RESULTS: Meta-analyses of NFE2L2 haplotypes showed association of haplotype GAGCAAAA, including the fully functional promoter haplotype AGC, with decreased risk (OR?=?0.8 per allele, p?=?0.012) and delayed onset (+1.1 years per allele, p?=?0.048) of Parkinson's disease. These results support the previously observed protective effect of this haplotype in the first study. Further, meta-analyses of the SNPs included in the haplotypes revealed four NFE2L2 SNPs associated with age at onset of Parkinson's disease (rs7557529 G?>?A, -1.0 years per allele, p?=?0.042; rs35652124 A?>?G, -1.1 years per allele, p?=?0.045; rs2886161 A?>?G, -1.2 years per allele, p?=?0.021; rs1806649 G?>?A, +1.2 years per allele, p?=?0.029). One of these (rs35652124) is a functional SNP located in the NFE2L2 promoter. No individual SNP was associated with risk of Parkinson's disease. CONCLUSION: Our results support the hypothesis that variation in the NFE2L2 gene, encoding a central protein in the cellular protection against oxidative stress, may contribute to the pathogenesis of Parkinson's disease. Functional studies are now needed to explore these results further.

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Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection.

Publications

Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection.

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