Final Activity Report Summary - HIVSNP (Host determinants of susceptibility to HIV-1 infection)
The natural course of HIV-1 infection is widely variable with extremes of disease progression within two years or continuous asymptomatic infection for more than 15 years. Moreover, certain people are relatively resistant to HIV-1 infection despite high levels of sexual risk behaviour. To identify host factors that influence this variability in outcome, we designed a genome-wide association study in the Amsterdam cohort studies on HIV infection and AIDS (ACS).
We tested approximately 300 000 single nucleotide polymorphisms (SNPs) in 335 HIV-1 infected homosexual men, 120 HIV-1 infected intravenous drug users and 50 HRSN. One SNP, rs1570023 in the C20orf151/Cables2 gene region, was significantly associated with HIV-1 disease course. Further in depth analysis of this large data set is likely to reveal additional associations. Apart from the identification of novel host factors, we also used this data set to confirm the reported association between SNPs in HLA-C and HCP5 gene regions with viral load at set point. Moreover, we found these SNPs to be correlated with HIV-1 disease course. The exact mechanism by which these SNPs, or the gene region they tag, influence disease progression remains to be established.
These results emphasise the importance of studying human genetic variations as a tool to find new host genetic factors in infectious diseases. GWA studies may reveal genes that can be considered new targets for drug development. In addition, SNPs strongly associated with HIV-1 disease progression, may be applied in routine diagnostics to predict the disease course and to determine for instance if antiviral therapy should be initiated early in infection. Indeed, screening for polymorphisms in the human genome that influence the course of infection may allow better fine-tuning of patient management.
We tested approximately 300 000 single nucleotide polymorphisms (SNPs) in 335 HIV-1 infected homosexual men, 120 HIV-1 infected intravenous drug users and 50 HRSN. One SNP, rs1570023 in the C20orf151/Cables2 gene region, was significantly associated with HIV-1 disease course. Further in depth analysis of this large data set is likely to reveal additional associations. Apart from the identification of novel host factors, we also used this data set to confirm the reported association between SNPs in HLA-C and HCP5 gene regions with viral load at set point. Moreover, we found these SNPs to be correlated with HIV-1 disease course. The exact mechanism by which these SNPs, or the gene region they tag, influence disease progression remains to be established.
These results emphasise the importance of studying human genetic variations as a tool to find new host genetic factors in infectious diseases. GWA studies may reveal genes that can be considered new targets for drug development. In addition, SNPs strongly associated with HIV-1 disease progression, may be applied in routine diagnostics to predict the disease course and to determine for instance if antiviral therapy should be initiated early in infection. Indeed, screening for polymorphisms in the human genome that influence the course of infection may allow better fine-tuning of patient management.