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Genetic acceleration of AIDS progression by a promoter variant of CCR5

  1. Author:
    Martin, M. P.
    Dean, M.
    Smith, M. W.
    Winkler, C.
    Gerrard, B.
    Michael, N. L.
    Lee, B.
    Doms, R. W.
    Margolick, J.
    Buchbinder, S.
    Goedert, J. J.
    O'Brien, T. R.
    Hilgartner, M. W.
    Vlahov, D.
    O'Brien, S. J.
    Carrington, M.

  2. Author Address

    O'Brien TR NCI, Lab Genom Divers Frederick, MD 21702 USA NCI, Lab Genom Divers Frederick, MD 21702 USA NCI, Sci Applicat Int Corp Frederick, MD 21702 USA Walter Reed Army Inst Res, Div Retrovirol Rockville, MD 20850 USA Univ Penn, Dept Pathol & Lab Med Philadelphia, PA 19104 USA Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol Baltimore, MD 21205 USA San Francisco Dept Publ Hlth San Francisco, CA 94102 USA NCI, Viral Epidemiol Branch Bethesda, MD 20892 USA Cornell Univ, Med Ctr, New York Hosp, Div Pediat Hematol & Oncol New York, NY 10021 USA
    1. Year: 1998
  2. Journal: Science
    1. 282
    2. 5395
    3. Pages: 1907-1911
  4. Type of Article: Article
  1. Abstract:

    The CCR5 gene encodes a cell surface chemokine receptor molecule that serves as the principal coreceptor, with CD4, for macrophage-tropic (R5) strains of human immunodeficiency virus-type 1 (HIV-1). Genetic association analysis of five cohorts of people with acquired immunodeficiency syndrome (AIDS) revealed that infected individuals homozygous for a multisite haplotype of the CCR5 regulatory region containing the promoter allele, CCR5P1, progress to AIDS more rapidly than those with other CCR5 promoter genotypes, particularly in the early years after infection. Composite genetic epidemiologic analyses of genotypes bearing CCR5P1, CCR5-Delta 32, CCR2-641, and SDF1-3'A affirmed distinct regulatory influences for each gene on AIDS progression. An estimated 10 to 17 percent of patients who develop AIDS within 3.5 years of HIV-1 infection do so because they are homozygous for CCR5P1/P1, and 7 to 13 percent of all people carry this susceptible genotype. The cumulative and interactive influence of these AIDS restriction genes illustrates the multigenic nature of host factors Limiting AIDS disease progression. [References: 48]

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