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Multicenter Study
. 2008;3(12):e3907.
doi: 10.1371/journal.pone.0003907. Epub 2008 Dec 24.

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

Affiliations
Multicenter Study

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 et al. PLoS One. 2008.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Genome wide association (GWA) study for plasma HIV-RNA levels in the ANRS PRIMO cohort.
Negative log10 (P)-values for the score test for genome-wide association across the genome ordered from 1pter to 22qter. Adjacent chromosomes are shown in light blue and dark blue. The spacing between SNPs does not reflect actual physical distances. The false discovery rate was calculated based on a stratified approach (by chromosome) leading to chromosome-specific thresholds.
Figure 2
Figure 2. Location of the twelve selected SNPs in the MHC region (6p21) and linkage disequilibrium plot.
Upper box shows an ideogram depicting chromosome 6 and the annotated region (transparent yellow rectangle). Lower box shows the linkage disequilibrium data matrix calculated from the European HapMap population. The colour intensity of each box is proportional to the strength of the LD property (r2) for the marker pair.
Figure 3
Figure 3. Boxplots for HIV-RNA levels in the PRIMO cohort for four major SNPs.
Plasma HIV-RNA level is highly correlated with the rs2395029 (HCP5), rs3093662 (TNF), rs13199524 and rs12198173 (TNXB) genotypes.
Figure 4
Figure 4. Boxplots for HIV-DNA levels in the PRIMO cohort for the three major SNPs.
Cellular HIV-DNA level is highly correlated with the rs2395029 (HCP5), rs6503919 (intergenic DDX40 – YPEL2) and rs2575735 (SDC2) genotypes.

References

    1. Ioannidis JP, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, et al. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3′A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med. 2001;135:782–795. - PubMed
    1. Kaslow RA, Carrington M, Apple R, Park L, Munoz A, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med. 1996;2:405–411. - PubMed
    1. Gao X, Bashirova A, Iversen AK, Phair J, Goedert JJ, et al. AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis. Nat Med. 2005;11:1290–1292. - PubMed
    1. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, et al. A whole-genome association study of major determinants for host control of HIV-1. Science. 2007;317:944–947. - PMC - PubMed
    1. Mellors JW, Rinaldo CR, Jr, Gupta P, White RM, Todd JA, et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996;272:1167–1170. - PubMed

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