title: Polymorphism of microsomal epoxide hydrolase is associated with chronic obstructive pulmonary disease and bronchodilator response.
abstract: OBJECTIVE
  Microsomal epoxide hydrolase (EPHX) is an important enzyme that metabolizes harmful reactive epoxides from smoking. Genetic variations of this enzyme are thought to increase the risk of developing chronic obstructive pulmonary disease (COPD). The aim of this study was to confirm and advance our knowledge of the role of this genetic variation in COPD. In addition, the association between this gene and important COPD-related phenotype bronchodilator responses (BDRs) was studied.
  
  
  METHODS
  This was a hospital-based case-control study. The EPHX1 genetic mutations of 105 smokers with COPD and 103 control smokers without COPD were evaluated by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. The association of genetic mutations and COPD phenotypes was also studied.
  
  
  RESULTS
  Subjects with EPHX1 113 (His(113)/His(113)) homozygote mutation had a strong correlation with COPD (odds ratio: 2.7, 95% confidence interval: 1.5-5.2). In addition, compared with other genotypes, the His(113) homozygote mutation patients had significantly lower BDRs, as shown by the absolute and percentage changes from baseline, in COPD patients (91.7 ± 12.5 mL vs. 141.6 ± 15.1 mL, p = 0.01 and 8.3 ± 1.2% vs. 13.4 ± 1.4%, p = 0.006).
  
  
  CONCLUSIONS
  A strong correlation between the EPHX1 113 mutant homozygote and smoking-related COPD was noted. This genetic polymorphism was also associated with lower BDRs in COPD patients.
authors: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, No. 138 Sheng-Li Road, Tainan 704, Taiwan.
authors: Chiung-Zuei
authors: CZ
authors: Chen
authors: Ru-Hsueh
authors: RH
authors: Wang
authors: Cheng-Hung
authors: CH
authors: Lee
authors: Chien-Chung
authors: CC
authors: Lin
authors: Han-Yu
authors: HY
authors: Chang
authors: Tzuen-Ren
authors: TR
authors: Hsiue
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects
chemical_list: D001993:Bronchodilator Agents; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human