A Common CD4 Gene Variant Is Associated with an Increased Risk of HIV-1 Infection in Kenyan Female Commercial Sex Workers
A Common CD4 Gene Variant Is Associated with an Increased Risk of HIV-1 Infection in Kenyan Female Commercial Sex Workers
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DOI：
10.1086/597616
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发表时间：
2009-05-01
影响因子：
6.4
通讯作者：
Fowke, Keith R.
中科院分区：
文献类型：
--
作者：
Oyugi, Julius O.;Vouriot, Francoise C. M.;Fowke, Keith R.
背景。据预测，CD4 C868T是一种新的CD4单核苷酸多态性（SNP），在非洲人群中高度流行，它改变了CD4的三级结构，这可能会改变对人类免疫缺陷病毒（HIV）感染的易感性。
方法。参与者来自肯尼亚的一个队列，包括87名未感染个体和277名HIV - 1感染个体。采用DNA测序来确定CD4基因型。用HIV - 1（IIIB）或肯尼亚原发性HIV - 1分离株感染表达相似水平野生型CD4或CD4 - Trp240的A2.01细胞以及来自未感染供体的外周血单个核细胞。采用HIV - 1 p24酶联免疫吸附测定来确定感染结果。
结果。发现CD4 C868T在HIV - 1感染参与者中比在HIV - 1未感染参与者中显著更为流行（P = 0.002），并且C868T也与HIV - 1感染发生率增加相关（P = 0.005，对数秩检验；P = 0.009，威尔科克森检验），优势比为2.49（P = 0.009）。体外和离体模型均表明CD4 C868T与对HIV - 1感染的易感性之间存在显著关联（分别为P = 0.001和P = 0.003）。
结论。总体而言，本研究发现CD4 C868T与对HIV - 1感染易感性增加之间存在很强的相关性。鉴于非洲人群中HIV感染和CD4 C868T的高流行率，这种SNP对非洲的疫情影响可能是巨大的。
Background. It has been predicted that CD4 C868T, a novel CD4 single-nucleotide polymorphism ( SNP) that has been found to be highly prevalent among Africans, changes the tertiary structure of CD4, which may alter susceptibility to human immunodeficiency virus (HIV) infection.Methods. Participants were from a Kenyan cohort and included 87 uninfected and 277 HIV-1-infected individuals. DNA sequencing was used to determine CD4 genotype. A2.01 cells expressing similar levels of either wild-type CD4 or CD4-Trp240 as well as peripheral blood mononuclear cells from uninfected donors were infected with HIV-1(IIIB) or a Kenyan primary HIV-1 isolate. HIV-1 p24 enzyme-linked immunosorbent assay was used to determine the outcome of infection.Results. CD4 C868T was found to be significantly more prevalent among HIV-1-infected participants than among HIV-1-uninfected participants (P = .002), and C868T was associated with an increased incidence of HIV-1 infection as well (P = .005, log-rank test; P = .009, Wilcoxon test), with an odds ratio of 2.49 (P = .009). Both in vitro and ex vivo models demonstrated a significant association between CD4 C868T and susceptibility to HIV-1 infection (P = .001 and P = .003, respectively).Conclusion. Overall, the present study found a strong correlation between CD4 C868T and increased susceptibility to HIV-1 infection. Given the high prevalence of both HIV infection and CD4 C868T in African populations, the effect of this SNP on the epidemic in Africa could be dramatic.