Association Between Polymorphisms Of TNF-? Gene And Susceptibility To HIV-1 Infection And CD4+T Cells After Treatment

Objective:As a proinflammatory cytokine,tumor necrosis factor-a?TNF-??plays a crucial role in inflammation,autoimmunity,malignant diseases and human immunodeficiency virus?HIV?infection,and gene polymorphism may a-ffect its production.The purpose of this study was to understand the relationship between TNF-?plasma level and the occurrence and development of HIV-1 inf-ection,as well as the relationship between TNF-?plasma level and the number of CD4+T cells after antiretroviral therapy.To investigate the correlation betwe-en TNF-?gene polymorphism at three loci rs1800629,rs361525 and rs1800630and genetic susceptibility to HIV-1 infection,as well as gene polymorphism and CD4+T cell recovery after antiretroviral therapy in HIV-1 patients.It provides n-ew genetic markers for the prevention of HIV-1 infection and targets for the occ-urrence,development,treatment and prevention of complications caused by HIV-1 infection.Methods:In this topic,the plasma TNF-?levels was detected by enzyme-linked immunosorbent assay?ELISA?method in 88 cases HIV-1 infected patie-nts?CD4+T cells>200/?l group 56 cases,CD4+T cells<200/?l group 32 cas-es?and control group 60 cases.The TNF-?concentration in each group was co-mpared.The correlation between plasma TNF-?level and HIV-1 infection was analyzed by rank sum test.The TNF-?gene single nucleotide polymorphism?S-NP?at rs1800629,rs361525 and rs1800630 of 248 HIV-1 infected patients and131 control patients were detected using the Snapshot method,and the results w-ere verified by the first-generation sequencing method.The Hardy-Weinberg eg-uiliberum of the three sites was detected by online software.Chi-square test was used to analyze the difference of genotype and allele frequency distribution bet-ween the case group and the control group.The Odds ratio?OR?and the corres-ponding 95%confidence interval^[1]were analyzed at the same time.The suscep-tible genotypes and alleles of HIV-1 infection were screened out.The haplotype analysis was carried out by online software SHEsis.Factors such as gender,age,baseline CD4+T cell count and treatment interval were adjusted by linear regres-sion to screen out genotypes and alleles that independently affected CD4+T cell count recovery after antiviral therapy for HIV-1 infection.Results:1.The genotype frequency distributions of TNF-?genes rs1800629,rs361525 and rs1800630 in the HIV-1 infection group and the control group were in a-ccordance with the harvean equilibrium?P>0.05?,which was representative of the population and comparable.2.The difference of plasma TNF-?level between HIV-1 infection group and control group was statistically significant?P<0.05?.Comparison of CD4+T cells>in the 200/?l group and the control group with CD4+T cells<200/?l group showed statistically significant difference in plasma TNF-?levels?P<0.05?,but there was no significant difference in plasma TNF-?levels between the CD4+T cells>200/?l group and the control group?P=0.304,P>0.05?.3.There were GG,GA and AA genotypes in TNF-?gene rs1800629 in the HIV-1 infection group.But in the control group,there were only two genotypes,GG and GA.Compared with the GG genotype,the GA genotype can increase the risk of HIV-1 infection?OR=2.456,95%CI:1.424-4.235,P=0.001?,the A allele also increases the risk of HIV-1 infection compared to the G allele?OR=2.367,95%CI:1.428-3.924,P=0.001?.After gender stratification,in the male population,the rs1800629 GA genotype significantly increased the risk of HIV-1infection?OR=3.247,95%CI:1.624-6.492,P=0.001?,and compared with the G allele,the A allele also increased the risk of HIV-1 infection?OR=2.728,95%CI:1.442-5.161,P=0.002?.In the female population,the effects of rs1800629 genotype,allele,dominant model and recessive model on the risk of HIV-1infection were not statistically significant.4.The TNF-?gene rs361525 site has only two genotypes,GG and GA.Only one heterozygous GA genotype was detected in the control group.Three heterozygous GA genotypes were detected in the case group,and the rest were all GG genotypes.5.There were three genotypes of TNF-?gene rs1800630,namely CC,CA and AA.The risk of HIV-1 infection was not related to each genotype,allele,dominant model CC vs CA+AA or recessive model CA+CC vs AA.After stratif-ication,no rs1800630 gene polymorphism was found to be associated with the risk of HIV-1 infection in either male or female populations.6.The AC haplotype of TNF-?gene rs1800629 and rs1800630 was associ-ated with the risk of HIV-1 infection?P=0.001,OR=2.259,95%CI=1.362-3.748?.7.After antiretroviral treatment,the CD4+T lymphocyte count of rs1800629 locus GA genotype was significantly lower than that of GG genotype?B=-70.736,95%CI:-119.706,-21.766,P=0.005?,the difference is statistically significant.The CD4+T lymphocyte counts in patients with the A allele were significantly lower than those in the G allele?B=-64.448,95%CI:-106.262,-22.635,P=0.003?,the difference was statistically significant.After gender stratification,CD4+T lymphocyte levels were lower in male patients with rs1800629 GA genotype and A allele after treatment,and CD4+T lymphocyte counts were lower in female pa tients with A allele after treatment.8.The effect of rs1800630 genotype and allele on the recovery of CD4+T lymphocyte count in HIV-1 patients after antiretroviral therapy was not statistic-ally significant.Conclusion:1.Plasma TNF-?levels in HIV-1 patients with CD4+T cells less than 200/?l were significantly higher than those in healthy controls and those with CD4+T cells more than 200/?l.2.The GA genotype and A allele of TNF-?gene rs1800629 can significan-tly increase the risk of HIV-1 infection in healthy men.3.The AC haplotype constructed by TNF-?gene rs1800629 and rs1800630increased the risk of HIV-1 infection.4.The A allele of TNF-?gene rs1800629 is an independent factor affecting poor recovery of CD4+T cells in HIV-1 patients after antiretroviral therapy.5.Male HIV-1 infected individuals carrying the TNF-?gene rs1800629 lo-cus GA genotype had poor recovery of CD4+T cells after antiretroviral therapy.6.There was no correlation between TNF-?gene rs1800630 and rs361525and the susceptibility to HIV-1 infection and recovery of CD4+T cell count after antiretroviral therapy.