Biology Faculty Articles

Title

Influence of CCR5 Promoter Haplotypes on AIDS Progression in African–Americans

Document Type

Article

Publication Date

9-29-2000

Publication Title

AIDS

Keywords

AIDS, Progression, Chemokine receptor, Genetic epidemiology, CCR5 promoter

ISSN

0269-9370

Volume

14

Issue/No.

14

First Page

2117

Last Page

2122

Abstract

Objectives: To test the hypothesis that the CCR5 promoter variants in HIV-1-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 asCCR5-2459A), 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 CCR2and CCR5 alleles. Survival analysis was used to assess the effect of CCR2, CCR5, andCCR5 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.

Comments

©2000 Lippincott Williams & Wilkins

Additional Comments

NCI contract #: NO1-CO-56000

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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