Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study

• Published in: PloS one 2008-12, Vol.3 (12), p.e3907-e3907
• Main Authors: Dalmasso, Cyril, Carpentier, Wassila, Meyer, Laurence, Rouzioux, Christine, Goujard, Cécile, Chaix, Marie-Laure, Lambotte, Olivier, Avettand-Fenoel, Véronique, Le Clerc, Sigrid, de Senneville, Laure Denis, Deveau, Christiane, Boufassa, Faroudy, Debré, Patrice, Delfraissy, Jean-François, Broet, Philippe, Theodorou, Ioannis
• Format: Article
• Language: English
• Subjects: Antiretroviral drugs; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Chromosome 17; Chromosome 8; Cohort Studies; Control; Cytotoxicity; Deoxyribonucleic acid; Development and progression; Disease Progression; DNA; DNA, Viral - metabolism; Drug therapy; Epidemiology; Female; Gene Frequency; Gene loci; Genes; Genetic diversity; Genetic factors; Genetic variance; Genetics and Genomics/Complex Traits; Genetics and Genomics/Genetics of Disease; Genetics and Genomics/Genetics of the Immune System; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Health aspects; Health services; Histocompatibility antigen HLA; HIV; HIV Infections - blood; HIV Infections - genetics; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - genetics; Human health and pathology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Hypotheses; Hypothesis testing; Infections; Infectious diseases; Life Sciences; Linkage Disequilibrium; Major histocompatibility complex; Male; Medical research; Metabolism; Plasma; Polymorphism, Single Nucleotide; Population; Public health; Quantitative Trait Loci - physiology; Ribonucleic acid; RNA; RNA, Viral - blood; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Syndecan; Virus replication; Y chromosomes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003907

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.