Multiple-cohort genetic asociation study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS

Sophie Limou, Cédric Coulonges, Joshua T. Herbeck, Daniëlle Van Manen, Ping An, Sigrid Le Clerc, Olivier Delaneau, Gora Diop, Lieng Taing, Matthieu Montes, Angélique B. Van't Wout, Geoffrey S. Gottlieb, Amu Therwath, Christine Rouzioux, Jean François Delfraissy, Jean Daniel Lelièvre, Yves Lévy, Serge Hercberg, Christian Dina, John PhairSharyne Donfield, James J. Goedert, Susan Buchbinder, Jérôme Estaquier, François Schächter, Ivo Gut, Philippe Froguel, James I. Mullins, Hanneke Schuitemaker, Cheryl Winkler, Jean François Zagurya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Background: The compilation of previous genomewide association studies of AIDS shows a major polymorphism in the HCP5 gene associated with both control of the viral load and long-term nonprogression (LTNP) to AIDS. Methods: To look for genetic variants that affect LTNP without necessary control of the viral load, we reanalyzed the genomewide data of the unique LTNP Genomics of Resistance to Immunodeficiency Virus (GRIV) cohort by excluding "elite controller" patients, who were controlling the viral load at very low levels (<100 copies/mL). Results: The rs2234358 polymorphism in the CXCR6 gene was the strongest signal (P=2.5×10-7; odds ratio, 1.85) obtained for the genomewide association study comparing the 186 GRIV LTNPs who were not elite controllers with 697 uninfected control subjects. This association was replicated in 3 additional independent European studies, reaching genomewide significance of Pcombined9.7×10 -10. This association with LTNP is independent of the combined CCR2-CCR5 locus and the HCP5 polymorphisms. Conclusions. The statistical significance, the replication, and the magnitude of the association demonstrate that CXCR6 is likely involved in the molecular etiology of AIDS and, in particular, in LTNP, emphasizing the power of extreme-phenotype cohorts. CXCR6 is a chemokine receptor that is known as a minor coreceptor in human immunodeficiency virus type 1 infection but could participate in disease progression through its role as a mediator of inflammation.

Original languageEnglish (US)
Pages (from-to)908-915
Number of pages8
JournalJournal of Infectious Diseases
Volume202
Issue number6
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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