Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression
Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression
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DOI：
10.1126/science.277.5328.959
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发表时间：
1997-08-15
期刊：
影响因子：
56.9
通讯作者：
OBrien, SJ
中科院分区：
文献类型：
--
作者：
Smith, MW;Dean, M;OBrien, SJ
趋化因子受体（CCR5 和 CXCR4）在人类免疫缺陷病毒 1 型（HIV-1）感染和发病机制中的关键作用促使人们寻找介导 HIV-1 疾病进展的其他趋化因子受体基因的多态性，CCR2 趋化因子和 HIV-1 受体基因的第一个跨膜区域内的突变（CCR2-64I）被描述为以 10 至 10 的等位基因频率发生。白人和非裔美国人中这一比例为 15%。对五个获得性免疫缺陷综合症 (AIDS) 队列（3003 名患者）的遗传关联分析显示，虽然 CCR2-64I 对 HIV-1 感染的发生率没有影响，但携带 CCR2-64I 等位基因的 HIV-1 感染者比普通等位基因纯合子的个体晚 2 至 4 年发展为艾滋病。由于 CCR2-64I 总是出现在带有 CCR5+ 的染色体单倍型上，因此确定了 CCR5-Delta 32（也延迟 AIDS 发病）和 CCR2-64I 的独立作用。据估计，疾病进展迅速（接触 HIV-1 后不到 3 年直至出现艾滋病症状）的 AIDS 患者中有 38% 至 45% 可归因于其 CCR2-+/+ 或 CCR5-+/+ 基因型，而 28% 至 29% 的长期幸存者（16 年或更长时间未患艾滋病）的存活率可归因于 CCR2 或 CCR5 的突变基因型。
The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression, A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta 32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.