The Polymorphism Of CCR5Δ32, CCR5m303a, CCR2-64I And Their Relation With AIDS Infection In Uygur HIV Highly-Infected Population

Objective:Taking the HIV Highly-Infected Uygur population in a certain city of Xinjiang as the object, the aim of our research is to thoroughly investigate the relation between the polymorphism of CCR5△32,CCR5m303a,CCR2-64I and the AIDS infection in the above-mentioned population.Methods:Based on current AIDS infection situation in Xinjiang, researchers choose AIDS highly-infected area as research spot and do horizontal survey by collecting demographic information and blood samples of the population. After protein-vestige experiments testing the 470 samples which are of complete information are divided into two groups:HIV positives and HIV negatives, acting as cases and contrasts in our research. Laboratory testing includes:extracting full blood gene group DNA, multi-layer PCR amplification, multi-fold LDR reaction and lastly testing genotype of CCR5△32,CCR5m303a,CCR2-64I in the case group and the contrast group by using sequence-testing instrument. We useχ2 to compare mutation frequency in different infection populations and to calculate relative hazard values in the three mutations, population attributive hazard values and their 95% validity period. It is also our main task to test if the genotype distribution of the contrast group conforms to Hardy-Weinberg balance. Linkage disequilibrium was analysed by SHEsis software.Results:In our research there are 470 examples of Uygur HIV highly-infected population, including 246 HIV positives (52.34%) and 224 HIV negatives. There are 260 male examples (55.32%) and 210 female examples (44.68%) with their average age of 32.11±6.43 years.1. The research result of CCR5△32 polymorphism shows that:the mutation frequency of CCR5△32 is 4.47%; in the HIV negative group, frequencies of wild type, heterozygous and homozygous CCR5 A32 are 93.30%,6.25% and 0.45% respectively; in the HIV positive group frequencies of them are 89.83%,9.76% and 0.41% respectively; after statistical examining, there is no statistical significance in the difference (χ2= 1.9681,P=0.374). There is not statistical significance of CCR5A32 in the population with different sexes.male (χ2=3.81, P=0.15).female (χ2=3.11, P=0.21)2. Frequencies of wild type, heterozygous and homozygous CCR5m303a in the HIV negative group are 98.21%,7.79%,0%, while these in the HIV positive group are 91.06%,8.94%,0% respectively. After statistical examining, there is statistical significance in the difference ((χ2=11.493, P=0.001). The mutation frequency of allelic CCR5m303a is 2.76%. There is statistical significance of CCR5m303a in the population with male (χ2=5.99, P=0.01),fenal is not (χ2=0.39, P=0.53)3. The mutation frequency of allelic CCR2-64I is 25.43%. Frequencies of wild type, heterozygous and homozygous CCR2-64I are 58.93%,36.16%,4.91% respectively, and these of the same gene in HIV positive group are 52.44%,39.84%,7.72% respectively. In the population the frequency of the allelic CCR2-64I mutation in the positive group (27.64%) is higher than that of negative group (22.99%). After statistical examining there is no statistical significance (P>0.05). there is not statistical significance of CCR5△32 in the population with different sexes.male (χ2=2.27, P=0.32),female (χ2=0.57, P=0.75)Conclusion:1. All these indicate that CCR5A32 mutation probably is not the protecting factor of AIDS infection and that this highly-infected population and the high-exposure environment are the main reasons for the high infection rate in Xinjiang.2. The mutation frequency of CCR5m303a in Xinjiang Uygur HIV highly-infected population is higher than that of other ethic groups, which indicates that the mutation of CCR5m303a probably is the risk factor of HIV-1 infection in the population.3. In the whole highly-infected Uygur population, which indicates there is no obvious influence of mutation of this gene on HIV infection and it is probably the co-receptor to resist HIV infection because of the co-operating effect with other mutations.4. There is probably no chain relation among CCR5△32,CCR5m303a and CCR2-64I mutations in Uygur HIV highly-infected population.