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  • Title: Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection.
    Author: van Manen D, Kootstra NA, Boeser-Nunnink B, Handulle MA, van't Wout AB, Schuitemaker H.
    Journal: AIDS; 2009 Jan 02; 23(1):19-28. PubMed ID: 19050382.
    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/mul. Both minor allele variants were independent predictors of disease progression, also when a CCR5 Delta32 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.
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