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Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12004-9.

Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.

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1
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.

Abstract

Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed.

PMID:
10518566
PMCID:
PMC18402
[Indexed for MEDLINE]
Free PMC Article
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