TRAF1/C5和TNF-α基因多态性与结核病易感性分析

Analysis of TRAF1/C5 and TNF-αgene polymorphisms with susceptibility to tuberculosis

目的分析肿瘤坏死因子受体相关蛋白1(tumor necrosis factor receptor-associated factor 1,TRAF1)/补体5(complement component 5,C5)rs10818488和肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)rs1800629基因多态性、环境因素及其交互作用对结核病(tuberculosis,TB)易感性的影响。方法选取TB多发家庭中TB确诊患者作为TB病例组,当地社区同期体检的健康志愿者作为健康对照(healthy controls,HC)组,与TB组有血缘关系且共同居住者组成家庭密切接触(healthy household contacts,HHC)组。采用logistic回归分析模型分析基因型和环境因素与TB的关联,叉生分析结合logistic回归分析模型分析基因与环境交互作用。结果年龄>45岁(χ^(2)=7.90,OR=2.28,95%CI:1.28~4.04,P=0.005)、吸烟(χ^(2)=15.27,OR=4.70,95%CI:2.16~10.22,P<0.001)增加HHC组TB发病风险。吸烟(χ^(2)=13.94,OR=3.58,95%CI:1.83~7.01,P<0.001)、居住地为农村(χ^(2)=25.05,OR=3.81,95%CI:2.26~6.42,P<0.001)和居室环境卫生较差(χ^(2)=15.31,OR=3.20,95%CI:1.79~5.73,P<0.001)增加HC组TB发病风险。TRAF1/C5 rs10818488位点中,携带AG基因型(共显性及超显性模型)、GG基因型(共显性模型)和AG-GG基因型(显性模型)增加HHC组和HC组患TB风险。TNF-αrs1800629位点与TB易感性暂未显示存在关联。分析基因与环境交互作用,在TB组和HHC组间,TRAF1/C5 rs10818488位点AG-GG基因型与吸烟存在协同作用;而在TB组和HC组间,rs10818488位点AG-GG基因型与吸烟和居室环境卫生较差存在协同作用,与居住地存在相乘交互作用,均使TB发病风险提高。结论TRAF1/C5 rs10818488位点的基因多态性可能与TB发病风险有关,且其与吸烟、居住地、居室环境卫生存在交互作用,共同影响TB的易感性。

Objective To analyze the effects of tumor necrosis factor receptor-associated factor 1(TRAF1)/complement component 5(C5)rs10818488 and tumor necrosis factor-alpha TNF-αrs1800629 gene polymorphisms,environmental factors,and their interactions on susceptibility to tuberculosis(TB).Methods The TB-confirmed patients in TB-prone families were selected as the case(TB)group.And the healthy volunteers who had medical checkups in the local community during the same period of time were selected as the healthy controls(HC)group.Besides and those who were related to the TB group and lived together were selected as the healthy household contacts(HHC)group.The association of genotype and environmental factors with TB was analyzed by a logistic regression analysis model,and the interaction between genes and environment was analyzed by crossover analysis combined with a logistic regression analysis model.Results Age above 45 years(χ^(2)=7.90,OR=2.28,95%CI:1.28-4.04,P=0.005),smoking(χ^(2)=15.27,OR=4.70,95%CI:2.16-10.22,P<0.001)increased the risk of TB prevalence in the HHC group.Smoking(χ^(2)=13.94,OR=3.58,95%CI:1.83-7.01,P<0.001),living in rural areas(χ^(2)=25.05,OR=3.81,95%CI:2.26-6.42,P<0.001),and poor living room sanitation(χ^(2)=15.31,OR=3.20,95%CI:1.79-5.73,P<0.001)increased the risk of TB prevalence in the HC group.Carriage of TRAF1/C5 rs10818488 AG genotype(co-dominant and hyper-dominant models),GG genotype(co-dominant model),and AG-GG genotype(dominant model)increased the risk of developing TB in the HHC and HC groups.No association between the TNF-αrs1800629 locus and TB susceptibility was found for the time being.Analyzing gene-environment interactions,there was a synergistic effect of the AG-GG genotype at the TRAF1/C5 rs10818488 locus with smoking between the TB and HHC groups,whereas there was a synergistic effect of the AG-GG genotype at the rs10818488 locus with smoking and poor living room sanitation,and a multiplicative interaction with the place of residence between the TB and HC groups,both of which increased the risk of TB prevelance.Conclusions Gene polymorphisms at the TRAF1/C5 rs10818488 locus may be associated with the risk of TB and interact with smoking,place of residence,and indoor sanitation to jointly influence susceptibility to TB.