中国南方汉族人种微粒体环氧化物酶基因多态性与吸烟者慢性阻塞性肺疾病易感性的相关性

目的　探讨中国南方汉族人的微粒体环氧化物酶 (mEPHX)基因多态性与吸烟者慢性阻塞性肺疾病 (COPD)易感性的关系。方法　将吸烟者分为 3组 :正常对照组 1秒钟用力呼气量占用力肺活量的百分率(FEV1/FVC % )≥ 70 % ,轻度COPD组FEV1/FVC %为≥ 5 0 %～ <70 % ,中、重度COPD组FEV1/FVC % <5 0 %。采集吸烟者的外周血或肺手术标本 ,常规抽提DNA ;采用PCR技术扩增mEPHX外显子 3和 4 ;分别以限制性内切酶EcoRV或RsaⅠ酶切外显子 3和外显子 4 ;以非变性聚丙烯酰胺凝胶电泳检测酶切片产物片段 ,观察mEPHX外显子 3和 4的基因多态性。结果　检测 5 1例吸烟者的mEPHX外显子 3和 74例吸烟者的mEPHX外显子 4的基因多态性 ,其中有 4 3例测定 2个外显子的基因多态性。COPD组外显子 3的等位基因突变纯合子检出率和突变检出率分别为 2 4 .14 % (7/ 2 9例 )和 86 .2 1% (2 5 / 2 9例 ) ,明显高于正常对照组的 9.0 9% (2 / 2 2例 )和 6 3.6 4 % (14 / 2 2例 ) ;3组间外显子 3等位基因多态性分布的差异有显著性 (P <0 .0 1)。COPD组外显子 4等位基因突变杂合子的检出率为 2 8.95 % (11/ 38例 ) ,低于正常对照组的 4 1.6 7% (15 / 36例 ) ,且 3组间外显子 4的突变杂合子分布的差异有显著性 (P <0 .0 0 5 )。 3组中外显子 3的

Relevance of microsomal epoxide hydrolase gene polymorphism and susceptibility to the development of chronic obstructive pulmonary disease

Objective To investigate the relevance of microsomal epoxide hydrolase gene polymorphism and susceptibility to the development of chronic obstructive pulmonary disease(COPD). Methods A PCR-based genoty- ping assay was used to screen the variant forms of mEPHX which conferred slow and fast activity in 22(36) blood donor controls and 29(38) patients with COPD. Results The distributions of the polymorphism of exon-3 and exon-4 mutations were significantly different among the three groups (P<0.01, 0.005). The proportion of the predicted very slow mEPHX activity in COPD group was higher than that in the control group (7/18 vs 0/15,P<0.005) and the proportion with the fast phenotype was lower (2/28 vs 3/15, P>0.05). Conclusions Genetic polymorphism of mEPHX may play a role in the individual susceptibility to the development of COPD. Epoxide derivatives of cigarette-smoking components may be the cause for some of the lung damages in COPD patients.