View All Abstracts for Session 27
146 The Genetics of Susceptibility to HIV/AIDS: Does Africa Differ?
V. Hayes*1, D. Petersen1, T. Cashmore1, T. Scriba1, H. Donninger1, M. Zeier1, E. Vardas2, A. Grimwood3, and E. Janse van Rensburg1
1Univ. of Stellenbosch, South Africa; 2Univ. of Witwatersrand, South Africa; and 3Chapel Street Community Hlth. Clin., Woodstock, South Africa
Background: Although the vast majority of people are susceptible to infection with HIV-1, rare individuals remain uninfected despite multiple high-risk exposures to the virus, some individuals have been shown to be partially resistant to the virus, with unusually slow progression to AIDS, whereas others show rapid disease progression. This led to the discovery of genetic factors involved HIV susceptibility. Most studies have been restricted to Caucasian populations and the analysis of a few so-called “Caucasian-related hotspot” variants, which are either rare or missing in the African population. We hypothesize that host susceptibility to HIV-infection and/or progression to AIDS within the African context, may not be as a result of a single (or small number) of yet unknown predisposing gene(s), but rather due to a large number of common but weaker genes that lead collectively to an individuals “risk profile.” To test this hypothesis 1 first has to identify African-based single nucleotide polymorphisms (SNPs).
Methods: Using the most powerful of the gel-based prescreening mutation detection systems currently available, namely denaturing gradient gel electrophoresis (DGGE), we have designed assays for the comprehensive analysis of the entire coding and/or promoter regions of 5 previously suggested (CCR5, CCR2, SDF-1, VDR, and NRAMP1) and 1 novel (AAT) candidate gene(s). Using these assays we have screened over 100 HIV seropositive and 100 seronegative controls from our predominantly African-ethnic population.
Results: Using these assays we identified previously reported and a large number of novel sequence variants in all genes analysed. The novel variants included both single possibly protective/causative variants and a number of African-based SNPs. We have analysed these, as well as previously reported SNPs, in over 300 patients, including HIV-seropositive slow, normal, and fast progressors, and high-risk-seronegative sex workers and discordant couples.
Conclusions: In this study, we have identified novel SNPs for use in phenotype-genotype association studies for the development of an African-based model of the polygenetic contribution to HIV/AIDS susceptibility.
Contact Author about this Abstract
