title: Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02).
abstract: To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P=6.79x10(-10); odds ratio, 3.47) and was possibly linked to an effect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P=3.02x10(-19)) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.
authors.affiliation: Conservatoire National des Arts et Métiers, Université Paris 7, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Limou
authors.forename: Sigrid
authors.initials: S
authors.lastname: Le Clerc
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulonges
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.forename: Taoufik
authors.initials: T
authors.lastname: Labib
authors.forename: Lieng
authors.initials: L
authors.lastname: Taing
authors.forename: Rob
authors.initials: R
authors.lastname: Sladek
authors.forename: Christiane
authors.initials: C
authors.lastname: Deveau
authors.forename: Rojo
authors.initials: R
authors.lastname: Ratsimandresy
authors.forename: Matthieu
authors.initials: M
authors.lastname: Montes
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Spadoni
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelièvre
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Amu
authors.initials: A
authors.lastname: Therwath
authors.forename: François
authors.initials: F
authors.lastname: Schächter
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D015894:Genome, Human; D005838:Genotype; D006679:HIV Seropositivity / Q000235:genetics; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D006680:HLA Antigens