Here's the Science abstract:
Genetic Acceleration of AIDS Progression by a
Promoter Variant of CCR5
Maureen P. Martin, Michael Dean, Michael W. Smith, Cheryl Winkler,
Bernard Gerrard, Nelson L. Michael, Benhur Lee, Robert W. Doms,
Joseph Margolick, * Susan Buchbinder, James J. Goedert,
Thomas R. O'Brien, Margaret W. Hilgartner, § David Vlahov,
Stephen J. O'Brien, ¶ Mary Carrington
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, CCR5-32, 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 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.
M. P. Martin, M. W. Smith, C. Winkler, B. Gerrard, M. Carrington, Science Applications International Corporation (SAIC),
National Cancer Institute, Frederick MD 21702, USA. M. Dean and S. J. O'Brien, Laboratory of Genomic Diversity, National
Cancer Institute, Frederick, MD 21702, USA. N. L. Michael, Division of Retrovirology, Walter Reed Army Institute of Research,
1600 East Gude Drive, Rockville, MD 20850, USA. B. Lee and R. W. Doms, Department of Pathology and Laboratory Medicine,
University of Pennsylvania, Philadelphia, PA 19104, USA. J. Margolick and D. Vlahov, Department of Epidemiology, Johns
Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA. S. Buchbinder, San Francisco Department of Public
Health, San Francisco, CA 94102, USA. J. J. Goedert and T. R. O'Brien, Viral Epidemiology Branch, National Cancer Institute,
6130 Executive Boulevard, Bethesda, MD 20892, USA. M. W. Hilgartner, Division of Pediatric Hematology and Oncology, New
York Hospital-Cornell Medical Center, New York, NY 10021, USA.
* 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@ncifcrf.gov
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