Report

Genetic Acceleration of AIDS Progression by a Promoter Variant of CCR5

Science  04 Dec 1998:
Vol. 282, Issue 5395, pp. 1907-1911
DOI: 10.1126/science.282.5395.1907

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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 CCR5regulatory region containing the promoter allele, CCR5P1, progress to AIDS more rapidly than those with other CCR5promoter genotypes, particularly in the early years after infection. Composite genetic epidemiologic analyses of genotypes bearingCCR5P1, CCR5-Δ32,CCR2-64I, 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 forCCR5P1/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.

  • * For the Multicenter AIDS Cohort Study (MACS).

  • For the San Francisco City Cohort.

  • For the Multicenter Hemophilia Cohort Study (MHCS).

  • § For the Hemophilia Growth and Development Study.

  • || For the AIDS Link to Intravenous Experience (ALIVE) Study.

  • To whom correspondence should be addressed. E-mail: obrien{at}ncifcrf.gov

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