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Genetic influence of CXCR6 chemokine receptor alleles on PCP-mediated AIDS progression among African Americans

Genes & Immunity volume 4, pages 245–250 (2003)Cite this article

Abstract

CXCR6 is a chemokine receptor and the primary coreceptor in SIV infection. A single nucleotide polymorphism 1469G→A, results in a nonconservative change in codon 3 (CXCR6-E3K) of the N-terminus of the coreceptor. To investigate the relation between the chemokine receptor CXCR6 genotype and progression to Pneumocystis carinii pneumonia (PCP) and from PCP to death, we clinically assessed and genotyped 805 individuals from an African-American injection drug-using cohort in Baltimore, MD, USA, for this CXCR6-E3K polymorphism. The allele frequency of CXCR6-3K was high (44%) in African Americans and rare in European Americans (f<1%). Although time to AIDS and PCP was similar for all CXCR6 genotypes, the median survival time from PCP to death for the CXCR6-3E/E and CXCR6-3E/K genotype was 1.5 years compared to 3.1 years for the CXCR6-K/K genotype. Individuals homozygous or heterozygous for the CXCR6-3E allele were 5.6 times more likely to die a PCP-mediated AIDS-related death than were individuals homozygous for CXCR6-3K. This study shows an association between CXCR6 genotype and progression from PCP to death among African-Americans with HIV. We suggest that CXCR6 may play a role in late-stage HIV-1 infection and may alter the progression to death after initial infection with PCP.

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Author notes

  1. Grant support: This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract No. NO1-CO-12400 and by the National Institute of Drug Abuse Grant DA04334. Disclaimer: The content of this publication does not necessarily reflect 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 US Government. Informed consent: Informed consent was granted by all patients and the Institutional Review Board of the Johns Hopkins School of Hygiene and Public Health approved all study and consent procedures.

    PD and PA contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    P Duggal, T H Beaty, S A Strathdee, H Farzadegan, L Johnson & D Vlahov

  2. Basic Research Program, SAIC-Frederick, National Cancer Institute, Frederick, MD, USA

    P An & C A Winkler

  3. Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    H Farzadegan & R B Markham

  4. Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, USA

    S J O'Brien

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  1. P Duggal
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  2. P An
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  3. T H Beaty
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  4. S A Strathdee
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  7. L Johnson
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  8. S J O'Brien
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  9. D Vlahov
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Duggal, P., An, P., Beaty, T. et al. Genetic influence of CXCR6 chemokine receptor alleles on PCP-mediated AIDS progression among African Americans. Genes Immun 4, 245–250 (2003). https://doi.org/10.1038/sj.gene.6363950

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  • DOI: https://doi.org/10.1038/sj.gene.6363950

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