CONCISE COMMUNICATION In¯uence of CCR5 promoter haplotypes on AIDS progression in African±Americans Ping An, Maureen P. Martin, George W. Nelson, Mary Carrington, Michael W. Smith, Kui Gong, David Vlahov a , Stephen J. O'Brien b and Cheryl A. Winkler Objectives: To test the hypothesis that the CCR5 promoter variants in HIV-1-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 seroinci- dent 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 unidenti®ed polymorphisms that may differ between racial groups. & 2000 Lippincott Williams & Wilkins AIDS 2000, 14:2117±2122 Keywords: AIDS, progression, chemokine receptor, genetic epidemiology, CCR5 promoter From the Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, the a Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, and the b Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland, USA. Sponsorship: Supported by Federal funds from the National Cancer Institute, National Institutes of Health, under contract No. NO1-CO-56000. Requests for reprints to: C. A. Winkler, Intramural Research Support Program, SAIC Frederick, National Cancer Institute- Frederick Cancer Research and Development Center, Bldg. 560, Room 11-64, Frederick, Maryland 21702-1201, USA. Note: The content of this publication does not necessarily re¯ect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. Received: 22 November 1999; revised: 21 March 2000; accepted: 3 May 2000. ISSN 0269-9370 & 2000 Lippincott Williams & Wilkins 2117