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Contrasting Genetic Influence of Ccr2 and Ccr5 Variants On Hiv-1 Infection and Disease Progression

  1. Author:
    Smith, M. W.
    Dean, M.
    Carrington, M.
    Winkler, C.
    Huttley, G. A.
    Lomb, D. A.
    Goedert, J. J.
    Obrien, T. R.
    Jacobson, L. P.
    Kaslow, R.
    Buchbinder, S.
    Vittinghoff, E.
    Vlahov, D.
    Hoots, K.
    Hilgartner, M. W.
    Obrien, S. J.

  2. Author Address

    Obrien SJ NCI VIRAL EPIDEMIOL BRANCH EXECUT PLAZA N 6130 EXECUT BLVD BETHESDA, MD 20892 USA NCI VIRAL EPIDEMIOL BRANCH BETHESDA, MD 20892 USA NCI SCI APPLICAT INT CORP FREDERICK FREDERICK, MD 21702 USA NCI LAB GENOM DIVERS FREDERICK, MD 21702 USA JOHNS HOPKINS MED INST SCH HYG & PUBL HLTH DEPT EPIDEMIOL BALTIMORE, MD 21205 USA UNIV ALABAMA DEPT EPIDEMIOL BIRMINGHAM, AL 35294 USA DEPT PUBL HLTH AIDS OFF SAN FRANCISCO, CA 94102 USA UNIV TEXAS SCH MED DEPT PEDIAT HOUSTON, TX 77030 USA UNIV TEXAS SCH MED DEPT INTERNAL MED HOUSTON, TX 77030 USA CORNELL UNIV MED CTR NEW YORK HOSP DIV PEDIAT HEMATOL & ONCOL NEW YORK, NY 10021 USA
    1. Year: 1997
  2. Journal: Science
    1. 277
    2. 5328
    3. Pages: 959-965
  4. Type of Article: Article
  1. Abstract:

    The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression, A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta 32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5. [References: 63]

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