TAP1基因多态性与被动吸烟的交互作用对肺结核发病的影响

Interaction between TAP 1 gene polymorphism and passive smoking on tuberculosis

目的TAP 1基因多态性与感染性疾病发生有关。文中探讨TAP 1基因多态性、环境危险因素及两者的交互作用对肺结核发病的影响。方法采用病例对照研究方法,选取广东省各个结核防治单位128例肺结核确诊患者为病例组,并选取同期145例体检健康人群作为对照组。采用多因素Logistic回归模型纳入乘积项法分析TAP 1基因多态性与被动吸烟的相乘交互作用,叉生分析法分析两者相加交互作用。采用SHEsis软件对TAP 1基因两位点进行单体型分析。结果单因素分析结果显示被动吸烟、TAP1rs1135216位点等位基因和基因型在病例组与对照组中的分布差异有统计学意义(P<0.05);rs1057141位点等位基因和基因型在病例组与对照组的分布差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示,rs1135216位点AG基因型(OR=7.320,95%CI:2.394~22.381)及被动吸烟(OR=1.978,95%CI=1.193~3.281)与肺结核发病有关。TAP1 rs1135216位点超显性模型(AA+GG vs AG)中,AG基因型(OR=6.528,95%CI=2.168~19.657)的肺结核发病风险是AA+GG基因型的6.528倍;显性模型(AG+GG vs AA)中,AG+GG基因型(OR=4.549,95%CI=1.888~10.963)的肺结核发病风险是AA基因型的4.549倍。TAP 1基因两位点单体型GG与肺结核发病存在关联(OR=3.439,95%CI:1.636~7.228)。rs1135216位点超显性模型中AG基因型、显性模型中AG+GG基因型与被动吸烟在肺结核发病中无相乘交互作用。叉生分析结果显示,携带AG基因型且有被动吸烟者肺结核患病风险是未携带AG基因型且无被动吸烟的20.811倍(OR=20.811,95%CI:2.586~167.501)。结论被动吸烟可增加肺结核患病风险。TAP1 rs1135216位点基因多态性与肺结核发病相关,且其与被动吸烟在肺结核发病中存在相加交互作用。TAP1 rs1057141位点基因多态性与肺结核发病无关,但其与rs1135216位点的单体型GG与肺结核发病相关。

Objective To explore the effects of TAP1 gene polymorphism,environmental risk factors and their interaction on the incidence of tuberculosis.Methods In the case control study,128 patients with tuberculosis confirmed in tuberculosis prevention and control units in Guangdong Province were selected as the case group,and 145 healthy people were selected as the control group during the same period.Multivariate Logistic regression analysis was adopted to analyze the multiplicative interaction between TAP1 gene polymorphism and passive smoke by products of coefficients,and cross-generation analysis to analyze the additive interaction.SHEsis software was used to analyze the haplotype of the two loci in TAP1 gene.Results Univariate analysis indicated that passive smoking,TAP1rs1135216 allele and genotype were significantly different between the 2 groups(P<0.05).rs1057141 allele and genotype and passive smoking were the same between the control group and the case group(P>0.05).Multivariate Logistic Regression Analysis showed that AG genotype at rs1135216 locus(OR=7.320,95%CI:2.394-22.381)and passive smoking(OR=1.978,95%CI=1.193-3.281)were associated with the incidence of tuberculosis.In the TAP1 rs1135216 superdominant model(AA+GG vs AG),the tuberculosis risk of AG genotype(OR=6.528,95%CI=2.168~19.657)was 6.528 times higher than that of AA+GG genotype.In the dominant model(AG+GG vs AA),the tuberculosis risk of AG+GG genotype(OR=4.549,95%CI=1.888~10.963)was 4.549 times higher than that of AA genotype.The haplotype GG at two loci of TAP1 gene is associated with the incidence of tuberculosis(OR=3.439,95%CI:1.636~7.228).There was no multiplicative interaction between Ag genotype in rs1135216 superdominant model and Ag+GG genotype in dominant model and passive smoking in the incidence of tuberculosis.The cross-generation analysis showed that the tuberculosis risk in passive smokers with AG genotype was 20.811 times higher than that in passive smokers without AG genotype(OR=20.811,95%CI:2.586~167.501).Conclusion Passive smoking increases the risk of tuberculosis.The TAP1 rs1135216 gene polymorphism is associated with the incidence of tuberculosis,and it has an additive interaction with passive smoking in the incidence of tuberculosis.The polymorphism of TAP1 rs1057141 locus was not associated with the incidence of tuberculosis,but the haplotype GG associated with rs1135216 was associated with the incidence of pulmonary tuberculosis.