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Multiple-Cohort Genetic Association Study Reveals CXCR6 as a New Chemokine Receptor Involved in Long-Term Nonprogression to AIDS

  1. Author:
    Limou, S.
    Coulonges, C.
    Herbeck, J. T.
    van Manen, D.
    An, P.
    Le Clerc, S.
    Delaneau, O.
    Diop, G.
    Taing, L.
    Montes, M.
    van't Wout, A. B.
    Gottlieb, G. S.
    Therwath, A.
    Rouzioux, C.
    Delfraissy, J. F.
    Lelievre, J. D.
    Levy, Y.
    Hercberg, S.
    Dina, C.
    Phair, J.
    Donfield, S.
    Goedert, J. J.
    Buchbinder, S.
    Estaquier, J.
    Schachter, F.
    Gut, I.
    Froguel, P.
    Mullins, J. I.
    Schuitemaker, H.
    Winkler, C.
    Zagury, J. F.

  2. Author Address

    [Limou, Sophie; Coulonges, Cedric; Le Clerc, Sigrid; Delaneau, Olivier; Diop, Gora; Taing, Lieng; Montes, Matthieu; Schaechter, Francois; Zagury, Jean-Francois] Chaire Bioinformat Conservatoire Natl Arts & Meti, Paris, France. [Coulonges, Cedric; Le Clerc, Sigrid; Rouzioux, Christine; Delfraissy, Jean-Francois; Zagury, Jean-Francois] French Agcy Res AIDS & Hepatitis, Agence Natil Rech, SIDA & Hepatites Virales Genom Grp, Paris, France. [Therwath, Amu] Univ Paris 07, Oncol Mol Lab, Paris, France. [Limou, Sophie; Le Clerc, Sigrid; Lelievre, Jean-Daniel; Levy, Yves; Estaquier, Jerome; Zagury, Jean-Francois] Univ Paris 12, INSERM, U955, Creteil, France. [Estaquier, Jerome] Hop Henri Mondor, AP HP, F-94010 Creteil, France. [Limou, Sophie; Gut, Ivo] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France. [Hercberg, Serge] UP13, Ctr Rech Nutr Humaine Ile de France, UMR U557, INSERM,U1125,Inra, Bobigny, France. [Dina, Christian; Froguel, Philippe] Inst Pasteur, UMR 8090, CNRS, F-59019 Lille, France. [van Manen, Danielle; van't Wout, Angelique B.] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Landsteiner Lab,Ctr Infect Dis & Immun Amsterdam, NL-1105 AZ Amsterdam, Netherlands. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Herbeck, Joshua T.; Gottlieb, Geoffrey S.; Mullins, James I.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [An, Ping; Winkler, Cheryl] NCI, Lab Genom Div, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Phair, John] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Donfield, Sharyne] Rho, Dept Biostat, Chapel Hill, NC USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA.;Zagury, JF, 292 Rue St Martin, F-75003 Paris, France.;zagury@cnam.fr
    1. Year: 2010
    2. Date: Sep
  2. Journal: Journal of Infectious Diseases
    1. 202
    2. 6
    3. Pages: 908-915
  4. Type of Article: Article
  5. ISSN: 0022-1899
  1. 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=2.5x10(-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 P-combined = 9.7x10(-10). This association with LTNP is independent of the 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.

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External Sources

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  2. DOI: 10.1086/655782
  3. View record in Web of Science®
  4. WOS: 000281091200013

Library Notes

  1. Fiscal Year: FY2009-2010
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