Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study

被引：150

作者：

Dalmasso, Cyril

Carpentier, Wassila ^{[2
]}

Meyer, Laurence ^{[3
]}

Rouzioux, Christine ^{[4
]}

Goujard, Cecile ^{[5
]}

Chaix, Marie-Laure ^{[4
]}

Lambotte, Olivier ^{[5
]}

Avettand-Fenoel, Veronique ^{[4
]}

Le Clerc, Sigrid ^{[6
]}

de Senneville, Laure Denis ^{[2
]}

Deveau, Christiane ^{[3
]}

Boufassa, Faroudy ^{[3
]}

Debre, Patrice ^{[2
]}

Delfraissy, Jean-Francois ^{[5
]}

Broet, Philippe ^{[1
,7
]}

Theodorou, Ioannis ^{[2
]}

机构：

[1] Univ Paris Sud, JE2492, Fac Med Paris Sud, Villejuif, France

[2] Univ Paris 06, INSERM, U543, AP HP, F-75252 Paris, France

[3] Univ Paris Sud, Fac Med Paris Sud, AP HP, Hop Bicetre, INSERM, Le Kremlin Bicetre, France

[4] Univ Paris 05, CHU Necker, AP HP, EA 3620, Paris, France

[5] Univ Paris Sud, Fac Med Paris Sud, AP HP, INSERM, U802, Le Kremlin Bicetre, France

[6] Conserv Natl Arts Metiers, Paris, France

[7] Univ Paris Sud, Hop Paul Brousse, AP HP, Serv Sante Publ, Villejuif, France

来源：

PLOS ONE | 2008年 / 3卷 / 12期

关键词：

D O I：

10.1371/journal.pone.0003907

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 49 条

[1] Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA [J].