Martin M P, Dean M, Smith M W, Winkler C, Gerrard B, Michael N L, Lee B, Doms R W, Margolick J, Buchbinder S, Goedert J J, O'Brien T R, Hilgartner M W, Vlahov D, O'Brien S J, Carrington M
Science Applications International Corporation (SAIC), National Cancer Institute, Frederick MD 21702, USA.
Science. 1998 Dec 4;282(5395):1907-11. doi: 10.1126/science.282.5395.1907.
The CCR5 gene encodes a cell surface chemokine receptor molecule that serves as the principal coreceptor, with CD4, for macrophage-tropic (R5) strains of human immunodeficiency virus-type 1 (HIV-1). Genetic association analysis of five cohorts of people with acquired immunodeficiency syndrome (AIDS) revealed that infected individuals homozygous for a multisite haplotype of the CCR5 regulatory region containing the promoter allele, CCR5P1, progress to AIDS more rapidly than those with other CCR5 promoter genotypes, particularly in the early years after infection. Composite genetic epidemiologic analyses of genotypes bearing CCR5P1, CCR5-Delta32, CCR2-64I, and SDF1-3'A affirmed distinct regulatory influences for each gene on AIDS progression. An estimated 10 to 17 percent of patients who develop AIDS within 3.5 years of HIV-1 infection do so because they are homozygous for CCR5P1/P1, and 7 to 13 percent of all people carry this susceptible genotype. The cumulative and interactive influence of these AIDS restriction genes illustrates the multigenic nature of host factors limiting AIDS disease progression.
CCR5基因编码一种细胞表面趋化因子受体分子，它作为主要的共受体，与CD4一起，作用于人类免疫缺陷病毒1型（HIV-1）的巨噬细胞嗜性（R5）毒株。对五个获得性免疫缺陷综合征（AIDS）患者队列进行的基因关联分析显示，携带含有启动子等位基因CCR5P1的CCR5调控区多位点单倍型纯合子的感染个体，比具有其他CCR5启动子基因型的个体更快发展为AIDS，尤其是在感染后的最初几年。对携带CCR5P1、CCR5-Δ32、CCR2-64I和SDF1-3'A基因型的综合遗传流行病学分析证实，每个基因对AIDS进展都有独特的调控影响。在HIV-1感染后3.5年内发展为AIDS的患者中，估计有10%至17%是因为他们是CCR5P1/P1纯合子，而所有人群中有7%至13%携带这种易感基因型。这些AIDS限制基因的累积和交互影响说明了限制AIDS疾病进展的宿主因素的多基因性质。
