pmc logo image
Logo of plosonePLoS OneView this ArticleSubmit to PLoSGet E-mail AlertsContact UsPublic Library of Science (PLoS)
Journal List > PLoS ONE > v.3(12); 2008

Formats:
PLoS ONE. 2008; 3(12): e3907.
Published online 2008 December 24. doi: 10.1371/journal.pone.0003907.
PMCID: PMC2603319
Copyright Dalmasso et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study
Cyril Dalmasso,#1 Wassila Carpentier,#2 Laurence Meyer,3 Christine Rouzioux,4 Cécile Goujard,5 Marie-Laure Chaix,4 Olivier Lambotte,5 Véronique Avettand-Fenoel,4 Sigrid Le Clerc,6 Laure Denis de Senneville,2 Christiane Deveau,3 Faroudy Boufassa,3 Patrice Debré,2 Jean-François Delfraissy,5 Philippe Broet,1,7 and Ioannis Theodorou2*
1JE2492, Faculty of Medicine Paris-Sud, Univ Paris-Sud, Villejuif, France
2CHU Pitié Salpetrière (AP-HP), INSERM U543, Université Pierre et Marie Curie, Paris, France
3INSERM, U822, Univ Paris-Sud, Faculté de Médecine Paris-Sud, AP-HP, Hopital Bicêtre, Epidemiology and Public Health Service, Le Kremlin-Bicêtre, France
4CHU Necker (AP-HP) EA 3620 Université Paris Descartes, Paris, France
5CHU Kremlin Bicêtre (AP-HP); INSERM, U802, Univ Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France
6Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France
7Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Paul Brousse, Service de Santé Publique, Univ Paris-Sud, Villejuif, France
Peter Sommer, Editor
Institut Pasteur Korea, Republic of Korea
#Contributed equally.
* E-mail: ioannis.theodorou/at/psl.ap-hop-paris.fr
These authors also contributed equally to this work.
Conceived and designed the experiments: WC LM CR PD JFD PB IT. Performed the experiments: WC MLC VAF SLC LDdS. Analyzed the data: CD LM CR CG OL JFD PB IT. Contributed reagents/materials/analysis tools: CD WC CG MLC OL VAF SLC CD FB JFD IT. Wrote the paper: CD LM CR PB IT.
Received July 3, 2008; Accepted November 3, 2008.
Small right arrow pointing to: This article has been cited by other articles in PMC.
Abstract
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.
Articles from PLoS ONE are provided here courtesy of
Public Library of Science