烟碱型乙酰胆碱受体基因多态性与慢性阻塞性肺疾病的相关性研究

Study on linkage between CHRNA5 gene polymorphism and susceptibility to chronic obstructive pulmonary disease

目的探讨烟碱型乙酰胆碱受体a5（CHRNA5）基因-1640C／T（rs3829787）单核苷酸多态性与慢性阻塞性肺疾病（COPD）易感性的关系。方法应用聚合酶链式反应和Sanger测序方法，检测135例COPD患者和131例健康对照者CHRNA5基因-1640C／T位点基因型分布情况，观察该位点基因多态性是否与COPD发病及严重程度相关。结果两组人群均存在CHRNA5基因-1640C／T多态性；两组人群基因型、等位基因频率差异存在显著统计学意义，COPD组CT＋TT基因型、T等位基因频率均高于对照组（P〈0．01）；基因型频率的相对风险分析结果发现，CT、TT基因型各自患COPD的风险分别是CC基因型的1．78倍（95％CI：O．98～3．33）和3．89倍（95％CI：1．04—14．57）；-1640C／T多态性在轻中度、重度COPD组间的分布差异无统计学意义（P〉0．05）；在轻度吸烟人群中携带T等位基因可能更容易发生COPD。结论CHRNA5基因-1640C／T多态性可能与COPD易感性相关，该位点携带T等位基因的轻度吸烟人群可能更容易发生COPD。

Objective To observe the polymorphism and gene frequency of nicotine acetylcholine receptor subunits alpha 5 （CHRNAS） gene-1640C/T（ rs3829787）, and that associate with susceptibihty to chronic obstructive pulmonary disease （COPD）. Methods With PCR-Sanger method, CHRNA5 gene- 1640C/T polymorphism was genotyped to 135 COPD patients and 131 healthy adults. Whether the genetic polymorphism of CHRNA5 gene was association with the degree of airway obstruction were investigated. Results There was CHRNA5 gene-1640C/T polymorphism in population. -1640CT ＋ TY genotype and T allele were more frequent in patients than in controls（P 〈 0.01 ）. The relative risk of CT genotype carrier to suffer from COPD was 1.78 times of CC genotype（95% CI：O. 98-5.33）. The relative risk of TY geno- type carrier to suffer from COPD was 3.89 times of CC genotype（95% CI：I. 04-14.57）. However,the dis- tribution of CHRNA5 gene-1640C/T polymorphism was no significant difference between mild and severe COPD patients （ P 〉 0.05 ）. Mild smokers who carried the T allele may be more susceptible to COPD. Conclusion CHRNA5 gene -1640T allele may be a genetic susceptibility factor to COPD.