CHRNA3基因启动子多态与吸烟人群慢性阻塞性肺疾病易感性研究

CHRNA3 gene promoter polymorphism with susceptibility to chronic obstructive pulmonary disease in smokers

目的探讨吸烟人群中尼古丁受体3（CHRNA3）基因启动子区的基因多态性与吸烟相关的慢性阻塞性肺疾病（COPD）易感性的关系。方法采用病例一对照研究方法，分别收集60例吸烟c0PD患者和60例健康吸烟者，采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术检测CHRNA3基因启动子单核苷酸多态位点rs6495309（T〉c）的基因型，用SPSS13．0软件进行非条件Logistic回归校正混杂因素的影响，分析基因变异与吸烟者的COPD的发病情况。结果基因型频率均符合Hardy-Weinberg平衡定律（P〉0．05）。CHRNA3rs6495309（T〉c）突变基因型与吸烟COPD患者：三个基因型在吸烟COPD组与吸烟健康组中的分布差异具有统计学意义，P=0．043。CHRNA3rs6495309的CC基因型与吸烟者COPD的易感性相关（P=0．014），且在男性吸烟人群中，rs6495309的CC基因型与COPD的相关性更明显，携带CC基因型的吸烟男性个体患COPD是TT型个体的4．22倍（OR=4．222，95％ CI为1．369～13．020，P=0．012），而TC基因型与COPD无相关性。而且随着吸烟指数的增加rs6495309的CC基因型在COPD患者中占的比例越高。但进一步根据COPD发病严重程度进行分析可得，rs6495309的CC基因型在Ⅲ、Ⅳ级COPD人群与Ⅰ、Ⅱ级COPD人群的差异无统计学意义，即rs6495309的CC基因型与COPD严重程度无相关性。结论CHRNA3基因启动子区多态性与吸烟男性的COPD易感性相关，且rs6495309的CC基因型与吸烟男性COPD的相关性更明显，与吸烟的严重程度呈正相关，但其与COPD的严重程度无相关性。

Objective In this study, smokers in the nicotine receptor 3 （CHRNA3） gene promoter region polymorphism and smoking-related chronic obstructive pulmonary disease （COPD） susceptibility. Methods A case-control study of smoking were collected 60 cases of patients with COPD and 60 healthy smokers, using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） to detect single gene CHRNA3 nucleotide polymorphism rs6495309 （T〉C） genotypes, with SPSS 13. 0 software for non-conditional logistic regression calibration confounding factors, analysis of genetic variation and incidence of COPD in smokers. Results The genotype frequencies were in Hardy-Weinherg equilibrium （P 〉 0.05）. CHRNA3 rs6495309 （T 〉 C） genotype with smoking COPD patients： three genotypes in smoking patients with COPD and healthy smoking group in the distribution of a statistically significant difference, P = 0. 043. CHRNA3 rs6495309 CC genotype associated with susceptibility to COPD in smokers （ P =0. 014）, and smoking in the male population, rs6495309 CC genotype associated with COPD, more obvious, the smoking men carrying the CC genotype individuals suffering from COPD is 4.22 times than the TT genotype （OR =4.222,95% CI for the 1.369-13.020, P =0.012）, and TC genotype not associated with COPD. And with the smoking index increase rs6495309 CC genotype was higher than it in the proportion of patients with COPD accounted for. However, the incidence of COPD severity according to further analysis available, rs6495309 CC genotype in III, IV-class people with COPD I , III grade COPD population difference was not statistically significant, the rs6495309 CC genotype is not associated with severity of COPD. Conclusions CHRNA3 gene promoter polymorphism has susceptibility to COPD male smokers,and the rs6495309 CC genotype has significant correlated with the susceptibility of COPD in male smokers. The change of CHRNA3 gene promoter polymorphism was positively correlated with the severity of smoking, but is not relevant with COPD severe degree.