103 Genetic factors defining resistance and susceptibility to HIV/AIDS

One of the priorities for fundamental biomedical science is the discovery of the molecular-genetic basis of HIV pathogenesis. The progress in this area widens the possibilities for further improvement of HIV/AIDS prevention and therapy approaches. In this framework we have studied the population distribution of CCR5 rs333, CCR2 rs1799864, SDF1 rs1801157, HCP5 rs2395029, HLA-C rs9264942 and HLA-B*5701 genetic polymorphisms associated with susceptibility to HIV and AIDS and antiviral drugs intolerance among 1120 seronegative individuals comprising 12 ethnically distinct groups inhabiting Russia, Belarus, Ukraine, Kazakhstan, Kyrgyzstan and Moldova [Pomors, Russians (Vologda and Pskov region), Belarus, Ukrainians, Gagauz, Udmurts, Tatars, Chechens, Kazakhs, Kyrgyz, Tuvinians]. The rs333 variant is represented at most in the population of Pomors. The homozygotes who have significantly lower risk of HIV infection comprising 3% of the population. The least frequency of CCR5 polymorphism was described for Chechens, Kazakhs, Kyrgyz, Tuvinians: 6%, 6%, 5%, and 2% correspondingly. The highest incidence of CCR2 polymorphism was described for Chechens, Kazakhs and Kyrgyz. The other alleles under study did not reveal significant differences in distribution. The protective effect of the studied polymorphisms in CCR5, CCR2, SDF1 genes is characterized as cumulative. Based on the frequencies of three-loci genotypes we have established the values of relative hazard of AIDS onset and relative hazard of AIDS-caused death for the populations under study. The risks fall in range 0.79–0.94 and 0.76–0.93, correspondingly. We have found that interpopulation genetic variability confers for statistically relevant differences in the hazards estimated.