Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02).
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.
Limou
Sophie
S
Conservatoire National des Arts et Métiers, Université Paris 7, Paris, France.
Le Clerc
Sigrid
S
Coulonges
Cédric
C
Carpentier
Wassila
W
Dina
Christian
C
Delaneau
Olivier
O
Labib
Taoufik
T
Taing
Lieng
L
Sladek
Rob
R
Deveau
Christiane
C
Ratsimandresy
Rojo
R
Montes
Matthieu
M
Spadoni
Jean-Louis
JL
Lelièvre
Jean-Daniel
JD
Lévy
Yves
Y
Therwath
Amu
A
Schächter
François
F
Matsuda
Fumihiko
F
Gut
Ivo
I
Froguel
Philippe
P
Delfraissy
Jean-François
JF
Hercberg
Serge
S
Zagury
Jean-François
JF
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
D006680:HLA Antigens