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

Enrique Gonzalez, Mike Bamshad, Naoko Sato, Srinivas Mummidi, Rahul Dhanda, Gabriel Catano, Sonia Cabrera, Megan McBride, Xuan Hien Cao, Gerald Merrill, Peter O'Connell, Donald W. Bowden, Barry I. Freedman, Stephanie A. Anderson, Elizabeth A. Walter, James S. Evans, Kevin T. Stephan, Robert A. Clark, Sanjay Tyagi, Seema S. AhujaMatthew J. Dolan, Sunil K. Ahuja

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12004-12009
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number21
DOIs
StatePublished - Oct 12 1999

ASJC Scopus subject areas

  • General

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