Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans
Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans
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DOI：
10.1097/00002030-200009290-00007
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发表时间：
2000-09-29
期刊：
影响因子：
3.8
通讯作者：
Winkler, CA
中科院分区：
文献类型：
--
作者：
An, P;Martin, MP;Winkler, CA
目的：为了检验HIV-1感染的非裔美国人中CCR 5启动子变体影响进展为AIDS的速率的假设，并确定CCR 5 P1等位基因和CCR 5 59029 A变体之间的连锁不平衡的程度（在此称为CCR 5 - 2459 A），这两种药物都已被证明独立地加速高加索人的艾滋病进展。我们使用生存分析，以评估CCR 5启动子变体在HIV-1血清事件高加索人和非洲裔American.Subjects和方法的影响：基因型确定为806高加索人和1067非洲裔美国人，其中包括700血清转换，在四个HIV/AIDS自然史队列研究。这些基因型用于确定CCR 2和CCR 5等位基因的连锁和单倍型。生存分析被用来评估CCR 2，CCR 5，和CCR 5启动子单倍型对进展到艾滋病的血清事件African-American.Results：调查的高加索人和非洲裔美国人表现出完整的连锁不平衡之间的CCR 5 P1和CCR 5 - 2459 A网站。复合CCR 5 P1单倍型（包括CCR 5 - 2459 A等位基因）显示与非洲裔美国人和高加索人队列中快速进展至AIDS终点相关，但该效应在高加索人中为隐性，在非洲裔美国人中为显性。这可能是由于调节基因的存在或尚未确定的多态性，可能不同的种族群体。(C)2000年利平科特威廉姆斯&威尔金斯。
Objectives: To test the hypothesis that the CCR5 promoter variants in HIV-l-infected African-Americans affect the rate of progression to AIDS and to determine the extent of linkage disequilibrium between the CCR5P1 allele and the CCR5 59029A variant (referred to here as CCR5-2459A), both of which have been shown independently to accelerate AIDS progression in Caucasians.Design: We used survival analysis to assess the effects of CCR5 promoter variants in HIV-1 seroincident Caucasians and African-Americans.Subjects and methods: Genotypes were determined for 806 Caucasians and 1067 African-Americans, which included 700 seroconverters, enrolled in four HIV/AIDS natural history cohort studies. These genotypes were used to determine linkage and haplotypes for CCR2 and CCR5 alleles. Survival analysis was used to assess the effect of CCR2, CCR5,and CCR5 promoter haplotypes on progression to AIDS in seroincident African-Americans.Results: A survey of Caucasians and African-Americans demonstrated complete linkage disequilibrium between CCR5P1 and CCR5-2459A sites. The composite CCR5P1 haplotype (including the CCR5-2459A allele) is shown to be associated with rapid progression to AIDS endpoints in both African-American and Caucasian cohorts, but the effect is recessive in Caucasians and dominant in African-Americans. This is probably due to the presence of modulating genes or as yet unidentified polymorphisms that may differ between racial groups. (C) 2000 Lippincott Williams & Wilkins.