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.
Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Received 4 August, 2008
Revised 10 October, 2008
Accepted 14 October, 2008
Correspondence to Professor Dr Hanneke Schuitemaker, Department of Experimental Immunology M01-120, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5668298; fax: +31 20 5669756; e-mail: firstname.lastname@example.org