Study About CISH,IFN-γ Gene Polymorphisms And Susceptibility To HIV Sex Exposure In Henan Han Population

BackgroundAIDS(acquired immunodeficienoy syndorme,AIDS)has been a global spread of human immunodeficiency virus infection. HIV susceptibility shows a substantial degree of individual heterogeneity, such as in the population there existed persons who highly exposed to HIV infected or uninfected.At present, studys about factors of HIV susceptibility mainly focused on genetic factors and immune factors, and had made some progression.But there were no clear explanations about mechanism and causes for high or low susceptibility to HIV infection.CISH(cytokine-inducible src homology2domain protein)was the first member of the SOCS family to be described.CISH regulated the signaling of a variety of cytokines, such as interleukin-2and interleukin-3etc,it appears to be critical for directly or indirectly regulating T-cell proliferation and survival.IFN-y was an important immune regulator and could activate T cells and NK cells,and promoted a variety of cells expressed MHC I class and II class molecular, the two gene played an important role in the human’s immune reaction to antivirus and adjust immune system. Studys about CISH gene polymorphism with HIV susceptibility at home and abroad has not been reported, relationship between IFN-y polymorphisms and HIV susceptibility remained controversial.Therefore, a case-control study was conducted to investigate the relationship between CISH and IFN-y gene polymorphisms and HIV susceptibility in Henan Han Population.ObjectiveTo test CISH and IFN-y gene polymorphisms, and discuss relationship between polymorphisms,gene-gene interaction and susceptibility to HIV sex exposed persons of a certain area in Henan han population.Material and Methods1.Subjects:54patients who was sexually transmitted HIV between spouses and63people who had sex exposure without protective between spouses but HIV negative were chosen as cases and controls in a certain area of Henan han province.2.Laboratory method:Genotype of rs175634.rs414171polymorphisms were detected by PCR-RFLP,while the rs2430561was detected by PCR-SSP. Distribution of genotype and allele frequency between cases and controls was compared by chi-square.Logistic regression analysis to calculate the OR value and95%CI by adjusting for age, sex, education and having sex times per week. Prediction about haplotypes of CISH gene two loci was computed by the SNPHAP2.1software. Chi-square was also used to compare the distribution of combinded genotypes, trend analysis of genotypes and alleles mutation in the number of CISH and IFN-y gene polymorphisms between case and control group.Results1.Relationship between CISH and IFN-y genetic polymorphism and susceptibility to HIV sex exposureSite rs175634:Compared with genotype AA.genotype AG GG and (AG+GG) had no statistical correlation with HIV sex exposure susceptibility, adjusted OR(95%CI)were1.07(0.47,2.41).0.30(0.39,2.19)and0.79(0.36,1.73).Compared to alleles A. G alleles was not the alleles that susceptility to HIV sex exposure infection (OR=1.37,95%CI:0.77-2.43).Site rs414171:Compared with genotype AA, genotype AT, TT and (AT+TT) had no statistical correlation with HIV sex exposure susceptibility, adjusted OR(95%CI)were respectively1.03(0.44,2.40)、1.82(0.57,5.79) and0.92(0.41,2.06). Compared with A alleles, T alleles was not the alleles that susceptility to HIV sex exposure infection (OR=1.12,95%CI:0.64-1.96).Site rs2430561:Compared with TT genotype, TA and (TA+TT) may increase the susceptibility risk to HIV sex exposure infection, OR(95%CI) were2.41(1.06,5.52) and2.49(1.17,5.30), adjusted OR(95%CI) were2.42(1.09,5.33)and2.56(1.17,5.62). And compared to T alleles, A alleles mutation may be the HIV sex exposed susceptibility alleles (OR=2.04,95%CI:1.03-4.05).2.CISH gene haplotype analysisCompared with haplotype AA, the haplotype AT, GA,and GT had no association with the risk of HIV sexual exposure susceptibility. OR(95%CI)were0.73(0.24,2.15), 1.88(0.24,16.65)and1.28(0.70,2.35).3.Combined genotype analysis about CISH and IFN-γChoose the combined genotype AA AA TT as reference genotype, we didn’t find any genotype that had association with the risk of HIV sexual exposure susceptibility.4.Trend analysis of the number of mutations in three sitesTrend analysis of gene loci mutations analysis:Choose the genotypeAA, AA or TT as the zero mutational genotype reference, we found no association between genotypes mutations (the number1,2,3) and sexually exposed HIV susceptibility(/=1.75,P>0.05).Trend analysis of quantity mutant alleles:Choose A, A or T alleles as the zero mutational allele reference, the number of four mutant alleles might increase the risk of HIV sex exposed infection, OR(95%CI)were15.00(1.31,394.98).The mutation alleles0,1,2,3,4and5number of mutations were not association with the increased risk of HIV sex exposure infection(x2=2.88,P>0.05).Conclusions1.The gene polymorphism of rs175634and rs414171sites in CISH might have no statistical correlation with HIV sex exposure susceptibility.2.The gene polymorphism of rs2430561in IFN-y, A allete was the risk factor of HIV sex exposure susceptibility,genotype TA and (TA+AA)might be the risk factors of susceptibility to HIV sex exposed,but needed further inspection in a large sample size.3.We didn’t discover any gene-gene interaction between sites of CISH gene haplotypes in rs175634, rs414171and combined genotype analysis between CISH and IFN-y.4.we did not discover the interaction between genotypes and alleles in the number of mutations trend analysis for rs175634,rs414171and rs2430561sites,but when the total number of mutations in six alleles was4,could increase the susceptibility risk of HIV sex exposure,but this still need further inspection in a large sample size.