Genetic Polymorphism Of The TNFSF/TNFRSF System And Intracellular DNA Receptor In Behcet’s Disease In Chinese Han

Background: Behcet’s disease(BD)is an inflammatory disorder with clusters of clinical symptoms involving multiple systems.Although BD is increasingly being recognized,investigated and effectively managed,its etiology remains unclear.It has multiple autoinflammatory features,including unprovoked episodes of inflammation in the absence of detectable antigen-specific T cells or autoantibodies,enhanced activity of neutrophilic granulocytes.Imbalance of immune homeostasis plays an important role in the pathogenesis of BD.The TNFRSF/TNFSF system and nucleic acid immunity play an important role in initiating and regulating the immune response and maintaining immune homeostasis.Objective: To investigate whether single nucleotide polymorphisms(SNPs)of the TNFRSF/TNFSF system and intracellular DNA receptor gene are associated with susceptibility to BD in Chinese Han.Methods: There were 1055 BD patients and 1829 healthy volunteers enrolled for a two-phase case-control study.27 SNPs of eight genes(TNFRSF/TNFSF)and 4 single nucleotide polymorphisms(SNPs)of two DNA sensor genes(IFI16,cGAS)were tested using MassARRAY iPLEX?technology.Data were analyzed using a Chi-square(χ2)test and Fisher’s exact calibration test.The Bonferroni correction was applied for multiple testing.A Pc< 0.05 was defined as statistically significant.Hardy-Weinbergequilibrium(HWE)analysis was performed by the Chi-square(χ2)test in healthy controls.As males were predominant in the BD patient group,a binary logistic regression analysis was performed to assess the influence of gender and age on the association of gene polymorphisms with BD.Results: A statistically significant higher frequency of the A allele and a lower frequency of the G allele of rs1800692 was found in BD(Pc=0.013,OR= 1.233,95% CI= 1.103-1.379: Pc= 0.013,OR= 0.811,95% CI=0.725-0.907,respectively).The logistic regression analysis of the combined population confirmed our earlier finding that the AA genotype and A allele of rs1800692 were associated with a higher BD risk(AA vs GG: OR =1.326,95% CI =1.036-1.696,P = 0.025;A vs G: OR = 1.153,95% CI=1.021-1.302,P = 0.022,respectively).A higher frequency of TA genotype of rs1057028 was increased in BD.However,the significance was lost after Bonferroni correction(P= 0.011,OR= 1.411,95%CI= 1.082-1.839).There was no significant difference in allelic and genotypic frequencies for other candidate SNPs in BD compared with the controls.Conclusions: Our findings indicate that TNFRSF1 A might confer genetic susceptibility to BD in a Chinese Han population.The four candidate SNPs sites IFI16(rs2276404,rs1057028,rs6940)and cGAS(rs7761170)are not the susceptible sites of BD in Chinese han population.