TAP2基因多态性与肺结核易感性的病例对照家系研究

  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。

Relationship between TAP2 gene polymorphism and susceptibility to pulmonary tuberculosis based on a case-control family study

  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.