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Polymorphism in the development of COPD ( 16, 17). The remaining studies reported a protective effect for this Reported an association with disease severity rather than Number of studies have been performed to assess the associationīetween the EPHX1 polymorphisms and COPD in various populations Increased susceptibility to COPD and EPHX1 113 His-His homozygosity Since the initial report of an association between Various activities (fast, normal, slow and extremely slow) May be divided into four groups of putative EPHX1 phenotypes with These two single nucleotide polymorphisms (SNPs), the population The second, theĪ to G transition in exon 4 changes histidine (His) residue 139 toĪrginine (Arg) and produces an enzyme with an activity increased by Reducing the enzyme activity by ∼50% (slow allele). Responsible for the variable enzyme activity, conferring decreasedĪctivity by one mutation and increased activity by anotherģ changes tyrosine (Tyr) residue 113 to histidine (His), thus Reported that two common polymorphisms in the coding regions are The human EPHX1 gene is located onĬhromosome 1q42.1 and consists of nine exons. Varies as much as 50-fold in Caucasian populations ( 7). Epidemiological studies have shown thatĮPHX1 activity in the liver, lung and peripheral blood leucocytes Varying levels in the majority of tissues and cell types ( 6). Intermediates produced by cigarette smoke and is expressed at

Microsomal epoxide hydrolase (EPHX1) is an enzymeĮssential for the metabolism of the highly reactive epoxide Received more attention and become the focus of genetic COPD Protect the lung against smoke-induced oxidative stress have Smokers, oxidative stress caused by smoking is considered to be a Given that 95% of those who develop COPD are Genetic factors must be involved in the susceptibility andĭevelopment of COPD. Α1-antitrypsin deficiency, is rare in worldwide populations, other This, together with the familialĪs well as a susceptibility to frequent exacerbation in theseĪ genetic factor in the pathogenesis of COPD.Īs the only well-defined genetic factor of COPD, Only 10–15% of smokers develop the disease ( 3). Is widely accepted as the most significant risk factor for COPD, Predicted that it is likely to be the third leading cause of Increasing cause of morbidity and mortality worldwide ( 2). This is usually progressive and associated with anĪbnormal inflammatory response of the lungs to noxious particles or In addition, the results supported a contribution of EPHX1 to the aetiology of COPD.Ĭhronic obstructive pulmonary disease (COPD) is aĬomplex disease characterized by irreversible airflow limitation,Ībnormal permanent distal air-space enlargement and emphysema in A significant correlation between the two functional polymorphisms, T113C and A139G, of the EPHX1 gene and the enzyme activity and the individual's susceptibility to COPD was noted. Furthermore, a modest difference in the risk of COPD was observed between the subgroups by using the cigarette smokers or the non‑smokers as controls. The stratified analysis demonstrated this association in Caucasian but not in Asian individuals. Pooled analyses revealed that the extremely slow (OR, 1.77 95% CI, 1.23‑2.55) and slow EPHX1 enzyme activity (OR, 1.44 95% CI, 1.13‑1.85) were associated with an increased risk of COPD, while the fast enzyme activity was not associated with a decreased risk of COPD. The 139 mutant heterozygote was significantly associated with a decreased risk of COPD in Asian populations (OR, 0.82 95% CI, 0.68‑0.99) but not in Caucasian populations. The subgroup analyses demonstrated this association in Caucasian individuals (OR, 1.61 95% CI, 1.12‑2.31) but not in Asian individuals. The overall results showed that the EPHX1 113 mutant homozygote was significantly associated with an increased risk of COPD (OR, 1.33 95% CI, 1.06‑1.69). A total of 24 studies comprising 8,259 COPD patients and 42,883 controls were included. We performed a comprehensive meta‑analysis to clarify these findings.

However, the conclusions were controversial. Two functional polymorphisms of EPHX1, T113C and A139G, have been analyzed in numerous studies to assess the COPD risk attributed to these variants. Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the detoxification the products of smoking and is proposed to be a genetic factor for the development of chronic obstructive pulmonary disease (COPD).