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Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS.
Limou, Sophie; Coulonges, Cédric; Herbeck, Joshua T; van Manen, Daniëlle; An, Ping; Le Clerc, Sigrid; Delaneau, Olivier; Diop, Gora; Taing, Lieng; Montes, Matthieu; van't Wout, Angélique B; Gottlieb, Geoffrey S; Therwath, Amu; Rouzioux, Christine; Delfraissy, Jean-François; Lelièvre, Jean-Daniel; Lévy, Yves; Hercberg, Serge; Dina, Christian; Phair, John; Donfield, Sharyne; Goedert, James J; Buchbinder, Susan; Estaquier, Jérôme; Schächter, François; Gut, Ivo; Froguel, Philippe; Mullins, James I; Schuitemaker, Hanneke; Winkler, Cheryl; Zagury, Jean-François.
Afiliación
  • Limou S; Chaire de Bioinformatique, Conservatoire National des Arts et Métiers.
J Infect Dis ; 202(6): 908-15, 2010 Sep 15.
Article en En | MEDLINE | ID: mdl-20704485
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 x 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 P(combined)=9.7 x 10(-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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Virales / Síndrome de Inmunodeficiencia Adquirida / Receptores de Quimiocina / Sobrevivientes de VIH a Largo Plazo / Estudios de Asociación Genética Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: J Infect Dis Año: 2010 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Virales / Síndrome de Inmunodeficiencia Adquirida / Receptores de Quimiocina / Sobrevivientes de VIH a Largo Plazo / Estudios de Asociación Genética Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: J Infect Dis Año: 2010 Tipo del documento: Article Pais de publicación: Estados Unidos