Matheson Melanie C, Raven Joan, Walters E Haydn, Abramson Michael J, Ellis Justine A
Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia.
Hum Biol. 2006 Dec;78(6):705-17. doi: 10.1353/hub.2007.0015.
Microsomal epoxide hydrolase (EPHX1) is an important gene because of its role in the metabolism of components of cigarette smoke; thus it may be an important potential modifier of the risk of developing smoking-related lung disease, such as chronic obstructive pulmonary disease (COPD). Several studies have investigated EPHX1 and COPD, but some of these studies have potentially been affected by genotyping error. We investigated the influence of single nucleotide polymorphisms (SNPs) in EPHX1 on well-characterized COPD and intermediate phenotypes. A total of 1,232 participants completed a detailed respiratory questionnaire and spirometry. From this sample, 72 COPD cases (FEV1/FVC < 0.70 and FEV1 < 80% predicted) and 220 control subjects (no respiratory symptoms and normal lung function) were selected for analysis. The EPHX1 exon 3 and EPHX1 exon 4 polymorphisms were carefully genotyped to avoid error using several methods. We found that the EPHX1 exon 3 polymorphism was not associated with an increased risk of COPD, nor was the EPHX1 exon 4 polymorphism. In addition, none of the EPHX1 haplotypes were associated with an increased risk of any COPD phenotype. This finding, along with doubt shed on the accuracy of other studies that have demonstrated positive associations, suggests that a strong role for the EPHX1 polymorphisms in respiratory disease is unlikely.
微粒体环氧化物水解酶（EPHX1）是一个重要基因，因为它在香烟烟雾成分的代谢中发挥作用；因此，它可能是与吸烟相关的肺部疾病（如慢性阻塞性肺疾病，COPD）发病风险的一个重要潜在调节因子。多项研究已对EPHX1与COPD进行了调查，但其中一些研究可能受到基因分型错误的影响。我们研究了EPHX1单核苷酸多态性（SNP）对特征明确的COPD及中间表型的影响。共有1232名参与者完成了一份详细的呼吸问卷和肺活量测定。从这个样本中，选取了72例COPD病例（FEV1/FVC < 0.70且FEV1 <预测值的80%）和220名对照受试者（无呼吸道症状且肺功能正常）进行分析。使用多种方法对EPHX1外显子3和EPHX1外显子4多态性进行了仔细的基因分型以避免错误。我们发现EPHX1外显子3多态性与COPD风险增加无关，EPHX1外显子4多态性也无关。此外，EPHX1的单倍型均与任何COPD表型的风险增加无关。这一发现，连同对其他已证明存在正相关的研究准确性的质疑，表明EPHX1多态性在呼吸系统疾病中不太可能发挥重要作用。
