title: Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term nonprogression to AIDS.
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 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.
authors: Chaire de Bioinformatique, Conservatoire National des Arts et Métiers.
authors: Sophie
authors: S
authors: Limou
authors: Cédric
authors: C
authors: Coulonges
authors: Joshua T
authors: JT
authors: Herbeck
authors: Daniëlle
authors: D
authors: van Manen
authors: Ping
authors: P
authors: An
authors: Sigrid
authors: S
authors: Le Clerc
authors: Olivier
authors: O
authors: Delaneau
authors: Gora
authors: G
authors: Diop
authors: Lieng
authors: L
authors: Taing
authors: Matthieu
authors: M
authors: Montes
authors: Angélique B
authors: AB
authors: van't Wout
authors: Geoffrey S
authors: GS
authors: Gottlieb
authors: Amu
authors: A
authors: Therwath
authors: Christine
authors: C
authors: Rouzioux
authors: Jean-François
authors: JF
authors: Delfraissy
authors: Jean-Daniel
authors: JD
authors: Lelièvre
authors: Yves
authors: Y
authors: Lévy
authors: Serge
authors: S
authors: Hercberg
authors: Christian
authors: C
authors: Dina
authors: John
authors: J
authors: Phair
authors: Sharyne
authors: S
authors: Donfield
authors: James J
authors: JJ
authors: Goedert
authors: Susan
authors: S
authors: Buchbinder
authors: Jérôme
authors: J
authors: Estaquier
authors: François
authors: F
authors: Schächter
authors: Ivo
authors: I
authors: Gut
authors: Philippe
authors: P
authors: Froguel
authors: James I
authors: JI
authors: Mullins
authors: Hanneke
authors: H
authors: Schuitemaker
authors: Cheryl
authors: C
authors: Winkler
authors: Jean-François
authors: JF
authors: Zagury
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D056726:Genetic Association Studies; D020276:HIV Long-Term Survivors; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D011110:Polymorphism, Genetic; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology; D011991:Receptors, Virus / Q000235:genetics* / Q000276:immunology
chemical_list: C106330:CXCR6 protein, human; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus