编码 HIV-1 感染所需 HIV 依赖因子的基因变异的遗传关联。
Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection.
机构信息
National Cancer Institute, Rockville, MD, USA.
出版信息
J Infect Dis. 2010 Dec 15;202(12):1836-45. doi: 10.1086/657322.
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).
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.
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.
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.
摘要
背景
高通量全基因组技术促进了对细胞人类免疫缺陷病毒（HIV）感染中先前未知的宿主蛋白的鉴定。最近，3 项独立的研究使用小干扰 RNA 技术沉默人类基因组中的每个基因，以确定每个基因在 HIV 感染中的重要性。赋予显著效果的基因被称为 HIV 依赖性因子（HDF）。
方法
我们组装了 278 个 HDF 基因中的 6380 个单核苷酸多态性（SNP）的高密度面板，并在来自临床 AIDS 队列的 1633 个人中测试了基因型与 HIV 感染和 AIDS 进展的关联。
结果
经过多次测试的统计校正后，在 2 个基因 NCOR2 和 IDH1 中的 SNP 与 HIV 获得存在显著关联。在 TM9SF2 和 EGFR 基因内的 SNP 与 AIDS 进展的关联较弱。
结论
这项研究独立验证了 NCOR2 和 IDH1 对 HIV 传播的影响，其研究结果表明这些基因的变异会影响暴露个体对 HIV 感染的易感性。
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