Relationship between TAP2 gene polymorphism and susceptibility to pulmonary tuberculosis based on a case-control family study
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摘要:
目的 肺结核(pulmonary tuberculosis，PTB)感染具有个体差异性，研究抗原处理相关转运蛋白2(transporter-associated with antigen processing 2，TAP2)基因多态性对PTB发病的影响，并分析TAP2基因与人口学特征、行为因素、环境因素在PTB发病中的交互作用。 方法 使用病例对照家系研究方法，将广东省多个结核防治单位收集的PTB多发家系中确诊患者作为病例组(PTB组)，PTB多发家系中未患病者作为健康家庭密切接触者(healthy household contacts，HHC)组，当地同期收集的健康家系的家庭成员作为健康对照(healthy controls，HC)组。logistic回归分析模型分析各影响因素与PTB的关联，决策树(classification and regression tree, CART)模型分析发病危险因素间交互作用。 结果 logistic回归分析模型分析结果显示，对于HHC组，年龄、男性、吸烟和缺乏健身活动是PTB发病危险因素；对于HC组，城镇户口、BMI>18.5 kg/m2和室内干燥是发病保护因素，男性、吸烟、缺乏健身活动和室内环境卫生较差是PTB发病危险因素。PTB组与HHC组、HC组比较均发现rs3819721与PTB易感性相关。PTB组与HHC组的CART模型分析结果显示，不吸烟与有健身活动共存可降低PTB发病风险。PTB组与HC组模型分析结果显示，缺乏健身活动且携带rs3819721 AG+AA基因型的人群PTB患病风险更高。 结论 TAP2 rs3819721位点基因多态性与PTB发病相关，且其与缺乏健身活动在PTB发病中存在交互作用。暂未发现rs241447位点基因多态性与PTB发病有关。 -
关键词:
- 抗原处理相关转运蛋白2 /
- 基因多态性 /
- 肺结核
Abstract:Objective Pulmonary tuberculosis (PTB) infection has individual differences. To explore the effect of transporter-associated with antigen processing 2 (TAP2) gene polymorphism on pulmonary tuberculosis, and to analyze the interaction between TAP2 gene and demographic characteristics, behavioral factors and environmental factors in the pathogenesis of pulmonary tuberculosis. Methods Based on the case-control family study, patients with confirmed pulmonary tuberculosis in multiple pulmonary tuberculosis families collected by tuberculosis prevention and control units in Guangdong Province were selected as the case group. The healthy members in these families were included in the healthy household contacts (HHC) group, and the members of healthy families collected in the same period were included in the healthy controls (HC) group. Multivariate logistic regression model was used to analyze the association between the factors and pulmonary tuberculosis, and classification and regression tree (CART) model was used to analyze the interaction between risk factors of pulmonary tuberculosis. Results Multivariate logistic regression analysis showed that age, male, smoking and lack of fitness activities were risk factors of pulmonary tuberculosis for HHC group. For healthy controls, urban residence registration, BMI>18.5 kg/m2 and indoor dryness were protective factors of pulmonary tuberculosis, while, male, smoking, lack of fitness activities and poor indoor environmental sanitation were risk factors. There was a significant correlation between rs3819721 and susceptibility to tuberculosis between PTB group and HHC group, PTB group and HC group. The CART model of PTB group and HHC group showed that co-existence of no smoking and fitness activities could significantly reduce the risk of tuberculosis. The CART model of PTB group and HC group showed that people who lacked fitness activities and carried AG+AA genotype had a higher risk of tuberculosis. Conclusions The gene polymorphism of TAP2 rs3819721 is associated with pulmonary tuberculosis. And there is an interaction between TAP2 rs3819721 and lack of fitness activities in the pathogenesis of pulmonary tuberculosis. The gene polymorphism of rs241447 has not been found to be related to the pathogenesis of pulmonary tuberculosis. -
表 1 PTB发病危险因素的单因素分析[n(%)]
Table 1. Univariate analysis of risk factors of PTB [n(%)]
变量 PTB组(n=133) HHC组(n=107) HC组(n=173) PTB组vs. HHC组 PTB组vs. HC组 t/χ2值 P值 t/χ2值 P值 年龄(x±s, 岁) 43.7±16.1 34.1±19.7 41.9±14.8 4.132 0.001 0.991 0.322 性别 14.560 0.001 19.905 0.001 男 91(68.42) 47(43.93) 74(42.77) 女 42(31.58) 60(56.07) 99(57.23) 户口所在地 1.151 0.283 30.837 0.001 城镇 55(41.35) 37(34.58) 126(72.83) 农村 78(58.65) 70(65.42) 47(27.17) BMI(kg/m2) 0.950 0.330 12.777 0.001 ≤18.50 30(22.56) 30(28.04) 14(8.09) ＞18.50 103(77.44) 77(71.96) 159(91.91) 吸烟 32.888 0.001 32.097 0.009 是 67(50.38) 16(14.95) 34(19.65) 否 66(49.62) 91(85.05) 139(80.35) 喝酒 1.352 0.245 2.476 0.116 是 40(30.08) 25(23.36) 67(38.73) 否 93(69.92) 82(76.64) 106(61.27) 每周健身活动 6.463 0.011 40.439 0.001 是 42(31.58) 51(47.66) 118(68.21) 否 91(68.42) 56(52.34) 55(31.79) 室内采光情况 1.753 0.186 11.185 0.001 明亮 85(63.91) 77(71.96) 140(80.92) 较差 48(36.09) 30(28.04) 33(19.08) 室内潮湿情况 0.623 0.430 6.046 0.014 潮湿 104(78.20) 79(73.83) 113(65.32) 干燥 29(21.80) 28(26.17) 60(34.68) 室内环境卫生 1.352 0.245 10.063 0.002 良好 93(69.92) 82(76.64) 147(84.97) 较差 40(30.08) 25(23.36) 26(15.03) 
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表 2 PTB危险因素多因素logistic分析
Table 2. Multivariate logistic analysis of PTB risk factors
组别 变量 β值 sx值 OR(95% CI)值 χ2值 P值 PTB组vs. HHC组 年龄 0.036 0.009 1.036(1.019~1.054) 16.406 < 0.001 性别 男 1.296 0.319 3.653(1.956~6.823) 16.522 < 0.001 女 1.000 吸烟 是 1.966 0.362 7.144(3.511~14.536) 29.432 < 0.001 否 1.000 健身活动 是 1.065 0.325 2.900(1.534~5.484) 10.730 < 0.001 否 1.000 PTB组vs. HC组 性别 男 1.018 0.304 2.769(1.527~5.022) 11.242 < 0.001 女 1.000 户口所在地 城镇 -1.145 0.303 0.318(0.176~0.576) 14.297 < 0.001 农村 1.000 BMI(kg/m2) ≤18.50 1.000 >18.50 -1.193 0.433 0.303(0.130~0.708) 7.612 0.006 吸烟 是 1.728 0.331 5.630(2.943~10.772) 27.254 < 0.001 否 1.000 健身活动 是 1.650 0.313 5.287(2.864~9.760) 28.342 < 0.001 否 1.000 室内采光情况 较差 0.689 0.374 1.993(0.957~4.150) 3.392 0.066 明亮 1.000 室内潮湿情况 干燥 -1.062 0.397 0.346(0.159~0.753) 7.151 0.007 潮湿 1.000 室内环境卫生 较差 1.022 0.411 2.779(1.241~6.224) 6.174 0.013 良好 1.000
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表 3 TAP2基因遗传多态性与PTB易感分析[n(%)]
Table 3. Correlation analysis between the TAP2 locus genetic model and susceptibility to PTB [n(%)]
基因模型 基因型/等位基因 PTB组 HHC组 HC组 PTB组vs. HHC组 PTB组vs. HC组 χ2/OR(95% CI)值 P值 χ2/OR(95% CI)值 P值 rs3819721 GG 61(45.86) 71(66.36) 124(71.68) 10.519 0.005 21.142 0.001 AG 58(43.61) 31(28.97) 41(23.70) AA 14(10.53) 5(4.67) 8(4.62) G 180(67.67) 173(80.84) 289(83.53) 10.574 0.001 21.117 0.001 A 86(32.33) 41(19.16) 57(16.47) 共显性 GG 61(45.86) 71(66.36) 124(71.68) 1.000 1.000 AG 58(43.61) 31(28.97) 41(23.70) 2.336(1.204~4.530) 0.012 3.260(1.687~6.298) 0.001 AA 14(10.53) 5(4.67) 8(4.62) 2.159(0.605~7.710) 0.236 4.353(1.198~15.815) 0.025 显性 GG 61(45.86) 71(66.36) 124(71.68) 1.000 1.000 AG+AA 72(54.14) 36(33.64) 49(28.32) 2.309(1.225~4.352) 0.010 3.404(1.815~6.385) 0.001 隐性 GG+AG 119(89.47) 102(95.33) 165(95.38) 1.000 1.000 AA 14(10.53) 5(4.67) 8(4.62) 1.482(0.433~5.075) 0.531 2.766(0.797~9.599) 0.109 超显性 GG+AA 75(56.39) 76(71.03) 132(76.30) 1.000 1.000 AG 58(43.61) 31(28.97) 41(23.70) 2.127(1.116~4.056) 0.022 2.814(1.482~5.342) 0.002 rs241447 TT 63(47.37) 42(39.25) 83(47.98) 1.588 0.452 0.222 0.895 TC 58(43.61) 54(50.47) 72(41.62) CC 12(9.02) 11(10.28) 18(10.40) T 184(69.17) 138(64.49) 238(68.79) 1.180 0.277 0.011 0.918 C 82(30.83) 76(35.51) 108(31.21) 共显性 TT 63(47.37) 42(39.25) 83(47.98) 1.000 1.000 TC 58(43.61) 54(50.47) 72(41.62) 0.539(0.279~1.042) 0.066 1.241(0.673~2.288) 0.489 CC 12(9.02) 11(10.28) 18(10.40) 0.621(0.210~1.838) 0.389 1.165(0.377~3.598) 0.791 显性 TT 63(47.37) 42(39.25) 83(47.98) 1.000 1.000 TC+CC 70(52.63) 65(60.75) 90(52.02) 0.552(0.293~1.040) 0.066 1.229(0.683~2.213) 0.492 隐性 TT+TC 121(90.98) 96(89.72) 155(89.60) 1.000 1.000 CC 12(9.02) 11(10.28) 18(10.40) 0.866(0.314~2.389) 0.781 1.049(0.353~3.113) 0.932 超显性 TT+CC 75(56.39) 53(49.53) 101(58.38) 1.000 1.000 TC 58(43.61) 54(50.47) 72(41.62) 0.592(0.318~1.102) 0.098 1.214(0.673~2.189) 0.519
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表 4 PTB发病危险因素交互作用的CART模型分析
Table 4. CART model analysis of the interaction between risk factors of PTB
组别 节点 变量 频数[n(%)] OR(95%CI)值 P值 PTB组vs. HHC组 吸烟 健身活动 3 否 是 59(24.58) 1.000 4 否 否 98(40.83) 4.470(2.020~9.895) 0.001 1 是 83(34.58) 18.639(7.548~46.028) 0.001 PTB组vs. HC组 健身活动 性别 rs3819721显性模型 4 是 女 79(25.82) 1.000 3 是 男 81(26.47) 2.549(1.015~6.401) 0.046 6 否 GG 86(28.10) 1.000 5 否 AG+AA 60(19.61) 5.796(2.289~14.677) 0.001
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