title: Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.
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.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gonzalez
authors.forename: M
authors.initials: M
authors.lastname: Bamshad
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Mummidi
authors.forename: R
authors.initials: R
authors.lastname: Dhanda
authors.forename: G
authors.initials: G
authors.lastname: Catano
authors.forename: S
authors.initials: S
authors.lastname: Cabrera
authors.forename: M
authors.initials: M
authors.lastname: McBride
authors.forename: X H
authors.initials: XH
authors.lastname: Cao
authors.forename: G
authors.initials: G
authors.lastname: Merrill
authors.forename: P
authors.initials: P
authors.lastname: O'Connell
authors.forename: D W
authors.initials: DW
authors.lastname: Bowden
authors.forename: B I
authors.initials: BI
authors.lastname: Freedman
authors.forename: S A
authors.initials: SA
authors.lastname: Anderson
authors.forename: E A
authors.initials: EA
authors.lastname: Walter
authors.forename: J S
authors.initials: JS
authors.lastname: Evans
authors.forename: K T
authors.initials: KT
authors.lastname: Stephan
authors.forename: R A
authors.initials: RA
authors.lastname: Clark
authors.forename: S
authors.initials: S
authors.lastname: Tyagi
authors.forename: S S
authors.initials: SS
authors.lastname: Ahuja
authors.forename: M J
authors.initials: MJ
authors.lastname: Dolan
authors.forename: S K
authors.initials: SK
authors.lastname: Ahuja
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000349:Africa; D000368:Aged; D000483:Alleles; D001208:Asia; D005075:Biological Evolution; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006679:HIV Seropositivity / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D044469:Racial Groups / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D013997:Time Factors; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D019713:Receptors, CCR5