Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans

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 d etermine the extent of linkage disequilibrium between the CCR5P1 allele and the CCR5 59029A variant (referred to here as CCR5-2459A), both of which ha ve been shown independently to accelerate AIDS progression in Caucasians. Design: We used survival analysis to assess the effects of CCR5 promoter va riants 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 determin e linkage and haplotypes for CCR2 and CCR5 alleles. Survival analysis was u sed to assess the effect of CCR2, CCR5,and CCR5 promoter haplotypes on prog ression 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 associate d with rapid progression to AIDS endpoints in both African-American and Cau casian cohorts, but the effect is recessive in Caucasians and dominant in A frican-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.