Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study.
Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor genetic variants influence disease progression and early viral load. We performed a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters for detection of novel genetic factors that influence plasma HIV-RNA and cellular HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were localised in the 6p21 major histocompatibility complex (MHC) region and were in the vicinity of class I and III genes. Moreover, protective alleles for four disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and rs3093662) were strikingly over-represented among forty-five Long Term HIV controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV reservoir) are associated with the same four SNPs, but also with two additional SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and YPEL2 genes) and chromosome 8 (rs2575735; within the Syndecan 2 gene). Our data provide evidence that the MHC controls both HIV replication and HIV reservoir. They also indicate that two additional genomic loci may influence the HIV reservoir.
Dalmasso
Cyril
C
JE2492, Faculty of Medicine Paris-Sud, Univ Paris-Sud, Villejuif, France.
Carpentier
Wassila
W
Meyer
Laurence
L
Rouzioux
Christine
C
Goujard
Cécile
C
Chaix
Marie-Laure
ML
Lambotte
Olivier
O
Avettand-Fenoel
Véronique
V
Le Clerc
Sigrid
S
de Senneville
Laure Denis
LD
Deveau
Christiane
C
Boufassa
Faroudy
F
Debré
Patrice
P
Delfraissy
Jean-François
JF
Broet
Philippe
P
Theodorou
Ioannis
I
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000502:physiology*; D012367:RNA, Viral / Q000097:blood*
D004279:DNA, Viral; D012367:RNA, Viral