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. 2010 Dec 15;202(12):1836-45.
doi: 10.1086/657322.

V体育2025版 - Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection

Leslie W Chinn  1 , Minzhong Tang, Bailey D Kessing, James A Lautenberger, Jennifer L Troyer, Michael J Malasky, Carl McIntosh, Gregory D Kirk, Steven M Wolinsky, Susan P Buchbinder, Edward D Gomperts, James J Goedert, Stephen J O'Brien
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Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection (V体育2025版)

Leslie W Chinn et al. J Infect Dis. .

Abstract

Background: 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). VSports手机版.

Methods: 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. V体育安卓版.

Results: 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 V体育ios版. .

Conclusions: 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 VSports最新版本. .

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Figures

Figure 1
Figure 1
Genotype distribution for single-nucleotide polymorphisms that are highly associated with human immunodeficiency virus (HIV) infection. A, Seroconverters (SC) were significantly more likely to carry the variant T allele for rs1794942 in the NCOR2 gene, compared with high-risk HIV-exposed uninfected subjects (HREU) (A). The dominant model is shown. In a codominant genetic model for rs7578859 (located near the IDH1 gene), the variant C allele conferred protection against HIV infection in a dose-dependent manner, with 2 copies of the C allele providing the highest degree of protection (ie, the CC genotype was found at a higher frequency in HREU than in SC) and a single copy conferring less protection (B). OR, odds ratio.
Figure 2
Figure 2
Extended network and gene ontology analyses of human immunodeficiency virus (HIV)-dependency factors (HDFs) of interest. The results of the single-nucleotide polymorphism (SNP) associations tested in this study were examined in 2 subsets of genes: HDFs with curated interactions with HIV-1 and HDFs that demonstrated low-level significant associations with HIV/AIDS outcomes in our study. A, Network visualization of HDFs identified by Brass et al [5] associated (test-adjusted P < .05) with HIV infection in this study that are known to interact with HIV-1. Data from the IntAct protein-protein interaction database [–19] and the HIV-1, Human Protein Interaction Database [15, 16] were used to assemble networks in Cytoscape [20], with each edge representing a separate interaction. Shade intensity corresponds to the lowest P values for HIV infection in this study (Table 7, part A) for HDF genes, with dark gray indicating a smaller P value. Larger node size indicates that ⩾1 SNP in a gene was moderately associated with HIV infection. Gray diamonds represent HIV-1-encoded proteins. B, Same as panel A, but for AIDS progression. C, Functional groups (generated through clustering analysis performed using the DAVID tool) identified for genes containing SNPs with low-level infection and progression associations in this study. The negative logarithm of the P values of the functional terms associated with the clusters identified in the 60 infection HDFs are shown in white, whereas those associated with clusters found in the 53 AIDS progression genes are displayed in gray. The dotted line denotes statistical significance at −log (.05). EGF, epidermal growth factor; GPCRs, G protein-coupled receptors.
Table 1
Table 1
Association Analyses of HIV-Dependency Factors Identified by Multiple Functional Genomics Studies
Table 2
Table 2
Demographics of Study Populations Used in Human Immunodeficiency Virus (HIV)-Dependency Factor Gene Association Analyses
Table 3
Table 3
Statistical Hypotheses Used in Human Immunodeficiency Virus (HIV)-Dependency Factor Gene Association Analyses
Table 3
Table 3
Statistical Hypotheses Used in Human Immunodeficiency Virus (HIV)-Dependency Factor Gene Association Analyses
Table 4
Table 4
HIV-Dependency Factor Polymorphisms Genotyped in This Study
Table 5
Table 5
Human Immunodeficiency Virus (HIV)-Dependency Factor Single-Nucleotide Polymorphism (SNP) Associations with HIV Infection
Table 6
Table 6
Human Immunodeficiency Virus (HIV)-Dependency Factor Single-Nucleotide Polymorphism (SNP) Associations with AIDS Progression
Table 7
Table 7
Single-Nucleotide Polymorphisms in HIV-Dependency Factors Identified by Brass [5], Konig [6], and/or Zhou [7] with Unadjusted Infection or Progression Association of P < .05
Table 7
Table 7
Single-Nucleotide Polymorphisms in HIV-Dependency Factors Identified by Brass [5], Konig [6], and/or Zhou [7] with Unadjusted Infection or Progression Association of P < .05
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