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

  1. Author:
    An, P.
    Martin, M. P.
    Nelson, G. W.
    Carrington, M.
    Smith, M. W.
    Gong, K.
    Vlahov, D.
    O'Brien, S. J.
    Winkler, C. A.

  2. Author Address

    NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Bldg 560, Room 11-64, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Dev Ctr, Frederick, MD 21702 USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA.
    1. Year: 2000
  2. Journal: Aids
    1. 14
    2. 14
    3. Pages: 2117-2122
  4. Type of Article: Article
  1. Abstract:

    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 determine the extent of linkage disequilibrium between the CCR5P1 allele and the CCR5 59029A variant (referred to here as CCR5-2459A), 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 CCR2 and CCR5 alleles. Survival analysis was used to assess the effect of CCR2, CCR5,and CCR5 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. (C) 2000 Lippincott Williams & Wilkins.

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