Xie Jungang, Yang Shifang, Xu Yongjian, Zhang Zhenxiang
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the Public Health Ministry State Key Laboratory of Respiratory Diseases, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2009 Oct;29(5):551-6. doi: 10.1007/s11596-009-0505-6. Epub 2009 Oct 11.
The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC1), a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028); after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16-0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.
吸烟导致的DNA损伤可引起气道细胞凋亡和死亡，这可能与慢性阻塞性肺疾病（COPD）的发生有关。然而，仅有20%-30%的吸烟者会患COPD，这表明不同程度的DNA修复在吸烟者中会导致不同的结果。X射线修复交叉互补蛋白1（XRCC1）是一种碱基切除修复蛋白，在修复ROS介导的基础DNA损伤和单链DNA断裂方面具有多种作用。本研究调查了XRCC1（Arg399Gln）基因多态性与COPD易感性之间的关联。共招募了201例COPD患者和309名对照，并根据年龄和性别进行频率匹配。通过PCR-限制性片段长度多态性分析确定XRCC1基因型。总体而言，与XRCC1 Arg/Arg基因型个体相比，Trp/Trp基因型个体患COPD的风险无显著差异。然而，按吸烟状态分层后，在既往吸烟者中，与XRCC1 Arg/Arg基因型个体相比，Trp/Trp基因型个体患COPD的风险显著降低（调整后的OR=0.22，95%CI 0.06-0.85，P=0.028）；按吸烟暴露程度分层后，在轻度吸烟者中，与XRCC1 Arg/Arg基因型个体相比，Arg/Trp基因型和Trp/Trp基因型个体患COPD的风险显著降低（调整后的OR分别为0.39，95%CI 0.16-0.94，P=0.036；0.24，95%CI 0.07-0.79，P=0.019）。总之，XRCC1 Arg194Trp基因型与既往吸烟者和轻度吸烟者患COPD风险降低有关。
