AIDS

Skip Navigation LinksHome > January 2, 2009 - Volume 23 - Issue 1 > Association of HLA-C and HCP5 gene regions with the clinical...
AIDS:
doi: 10.1097/QAD.0b013e32831db247
Basic Science

Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection

van Manen, Daniëlle; Kootstra, Neeltje A; Boeser-Nunnink, Brigitte; Handulle, Muna AM; van't Wout, Angélique B; Schuitemaker, Hanneke

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Abstract

Background: Recently, a genome-wide association analysis revealed single-nucleotide polymorphisms (SNPs) in the gene regions of HLA-C and HCP5 to be associated with viral load at set point and SNPs in the RNF39/ZNRD1 gene region to be associated with HIV-1 disease course.

Methods: We studied whether the association of these SNPs with viral load at set point could be replicated and whether these SNPs also associated with other clinical outcomes of HIV-1 infection in 335 HIV-1-infected homosexual participants from the Amsterdam Cohort Studies on HIV infection and AIDS (ACS).

Results: Significant associations between the minor allele variants of SNPs HLA-C rs9264942 and HCP5 rs2395029 and a lower viral load at set point could be replicated in the ACS. Moreover, these SNPs were significantly associated with delayed progression to AIDS, AIDS-related death, and a CD4+ T-cell count below 400 cells/μl. Both minor allele variants were independent predictors of disease progression, also when a CCR5 Δ32 heterozygous genotype was included in the analysis. However, predictive value was not independent from viral load and CD4+ T-cell count at set point. The SNPs in the RNF39/ZNRD1 gene region were associated with set point CD4+ T-cell count but not with disease course in the ACS.

Conclusion: The minor allele variants of SNPs in the HLA-C and HCP5 gene regions are also in the ACS associated with a lower viral load at set point and additionally with delayed HIV-1 disease progression. The association of these SNPs with the relatively early course of infection may help unravel their mode of action.

© 2009 Lippincott Williams & Wilkins, Inc.

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