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Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
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Published on: December 27, 2010

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

P Duggal1, P An, T H Beaty

  • 1Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.

Genes and Immunity
|May 23, 2003
PubMed

Insights

The CXCR6-3K genetic variant is common in African Americans and associated with longer survival after Pneumocystis pneumonia (PCP) in HIV-infected individuals. This CXCR6 genotype may influence late-stage HIV progression.

Area of Science:

  • Immunology
  • Genetics
  • Virology

Background:

  • CXCR6 is a key coreceptor in SIV infection.
  • A specific polymorphism (CXCR6-E3K) alters the N-terminus of the CXCR6 coreceptor.
  • Pneumocystis pneumonia (PCP) is a common opportunistic infection in HIV/AIDS.

Purpose of the Study:

  • To investigate the association between CXCR6 genotype and PCP progression and survival in HIV-infected individuals.
  • To determine the role of the CXCR6-E3K polymorphism in disease progression and mortality.

Main Methods:

  • Clinical assessment and genotyping of 805 African-American injection drug users in Baltimore, MD.
  • Analysis of the CXCR6-E3K polymorphism and its correlation with time to AIDS, PCP, and survival post-PCP.
  • Comparison of allele frequencies between African Americans and European Americans.

Main Results:

  • The CXCR6-3K allele frequency was high (44%) in African Americans and rare (<1%) in European Americans.
  • No significant difference in time to AIDS or PCP across CXCR6 genotypes.
  • Median survival time from PCP to death was significantly longer for the CXCR6-K/K genotype (3.1 years) compared to CXCR6-3E/E and CXCR6-3E/K genotypes (1.5 years).
  • Individuals with CXCR6-3E alleles were 5.6 times more likely to die from PCP-mediated AIDS-related causes.

Conclusions:

  • CXCR6 genotype is associated with survival duration after PCP diagnosis in African-American HIV-infected individuals.
  • The CXCR6-3K allele confers a survival advantage post-PCP.
  • CXCR6 may influence late-stage HIV-1 infection progression and mortality.

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