微粒体环氧化物水解酶和谷胱甘肽S-转移酶P1编码基因多态性与慢性阻塞性肺疾病的关系。

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease.

作者信息

Xiao Dan, Wang Chen, Du Min-jie, Pang Bao-sen, Zhang Hong-yu, Xiao Bai, Liu Jing-zhong, Weng Xin-zhi, Su Li, Christiani David C

机构信息

Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing 100020, China.

出版信息

Chin Med J (Engl). 2004 May;117(5):661-7.

PMID:15161530

Abstract

BACKGROUND

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population.

METHODS

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5 (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy controls.

RESULTS

The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls.

CONCLUSIONS

mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.

摘要

背景

吸烟是慢性阻塞性肺疾病（COPD）的主要危险因素。然而，只有10% - 20%的慢性重度吸烟者会出现症状性疾病。COPD很可能是环境因素和遗传因素复杂相互作用的结果。COPD的遗传易感性可能取决于对香烟烟雾产物进行解毒的酶活性的变化，如微粒体环氧化物水解酶（mEH）和谷胱甘肽S - 转移酶（GST）。在本研究中，我们调查了编码mEH和谷胱甘肽S - 转移酶P1（GSTP1）的基因多态性与中国人群中COPD的关系。

方法

采用聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）技术，对100例COPD患者和100例年龄及性别匹配的健康对照者进行mEH第3外显子（Tyr113→His）、第4外显子（His139→Arg）多态性以及GSTP1第5外显子（Ile105→Val）多态性的检测。

结果

COPD患者中mEH第3外显子杂合子的比例显著高于对照组（42%对32%）。经年龄、性别、体重指数（BMI）和吸烟年限校正后的优势比（OR）为2.96（95%可信区间1.24 - 7.09）。COPD患者与对照组之间非常慢活性基因型与其他基因型相比无明显差异。当COPD患者为非吸烟者时，非常慢活性基因型与其他基因型的OR大于1.00；当COPD患者为吸烟者（现吸烟者和既往吸烟者）时，OR小于1.00。COPD患者与对照组之间经年龄、性别、BMI和吸烟校正后的GSTP1多态性无显著差异。