Smith C A, Harrison D J
Department of Pathology, University of Edinburgh, UK.
Lancet. 1997 Aug 30;350(9078):630-3. doi: 10.1016/S0140-6736(96)08061-0.
The first-pass metabolism of foreign compounds in the lung is an important protective mechanism against oxidative stress. We investigated whether polymorphisms in the gene for microsomal epoxide hydrolase (mEPHX), an enzyme involved in this protective process, had any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease (COPD) and emphysema.
We designed PCR-based genotyping assays to detect variant forms of mEPHX that confer slow and fast activity. We used these assays to screen 203 blood-donor controls and groups of patients with asthma (n = 57), lung cancer (n = 50), COPD (n = 68), and emphysema (n = 94), who were attending specialised clinics in Edinburgh, UK.
The proportion of individuals with innate slow mEPHX activity (homozygotes) was significantly higher in both the COPD group and the emphysema group than in the control group (COPD 13 [19%] vs control 13 [6%]; emphysema 21 [22%] vs 13 [6%]). The odds ratios for homozygous slow activity versus all other phenotypes were 4.1 (95% CI 1.8-9.7) for COPD and 5.0 (2.3-10.9) for emphysema.
Genetic polymorphisms in xenobiotic enzymes may have a role in individual susceptibility to oxidant-related lung disease. Epoxide derivatives of cigarette-smoke components may be the cause of some of the lung damage characteristic of these diseases.
肺部对外源化合物的首过代谢是抵御氧化应激的重要保护机制。我们研究了微粒体环氧化物水解酶（mEPHX）基因的多态性（该酶参与此保护过程）是否与个体患慢性阻塞性肺疾病（COPD）和肺气肿的易感性有关。
我们设计了基于聚合酶链反应（PCR）的基因分型检测方法，以检测赋予缓慢和快速活性的mEPHX变异形式。我们使用这些检测方法对203名献血者对照以及哮喘患者组（n = 57）、肺癌患者组（n = 50）、COPD患者组（n = 68）和肺气肿患者组（n = 94）进行筛查，这些患者均在英国爱丁堡的专科诊所就诊。
COPD组和肺气肿组中先天性mEPHX活性缓慢的个体（纯合子）比例显著高于对照组（COPD组13例[19%]对对照组13例[6%]；肺气肿组21例[22%]对13例[6%]）。COPD组纯合子缓慢活性相对于所有其他表型的比值比为4.1（95%置信区间1.8 - 9.7），肺气肿组为5.0（2.3 - 10.9）。
外源性物质代谢酶的基因多态性可能在个体对与氧化剂相关的肺部疾病的易感性中起作用。香烟烟雾成分的环氧化物衍生物可能是这些疾病某些肺部损伤特征的病因。
