The slow activity-associated genotype of microsomal epoxide hydroxylase-1 (m-EPHX-1) and low serum paraoxonase-1 (PON1) activity are associated with increased susceptibility to chronic obstructive pulmonary disease (COPD) in smokers

Abstract

Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease (COPD). We hypothesized that low serum activity level of paraoxonase-1 (PON1) that play a protective role in the lungs by metabolizing lipid peroxides and genetic polymorphism of antioxidant enzymes that detoxify cigarette smoke products such as microsomal epoxide hydroxylase-1 (m-EPHX-1) would be associated with increased susceptibility to COPD in smokers. The study was conducted on patients admitted to Chest Diseases Department, Kasr Al-Aini Hospital, Cairo University. Sixty subjects were divided into three groups—25 COPD patients, 25 chronic smokers without COPD, and 10 healthy nonsmokers. Pulmonary function tests were done for confirmation of COPD. Serum PON1 activity assay using spectrophotometric kinetic method and PCR-RFLP for genetic polymorphism of m-EPHX-1 exon 3 113 T>C were done to all participants. The significantly low median value for serum PON1 activity was found in COPD and smoker groups compared to the nonsmoker group (P = 0.015). Homozygote mutant genotype (HH) of m-EPHX-1 was present only in the COPD group compared to the other two groups with a frequency of 20%, 0%, and 0% respectively [P = 0.013; odds ratio (OR), 4.26; P = 0.008]. The OR between COPD and nonsmoker group was 14.222 (P = 0.008). The frequency of TH genotype was highest in the COPD group (44%, P = 0.013). While the wild genotype (TT) was more frequent in the nonsmoker group compared to the smokers and COPD groups (80%, 64%, and 36% respectively; P = 0.013). The slow m-EPHX-1 exon 3 polymorphisms (HH and HT) and the reduced serum PON1 activity are associated with higher susceptibility to COPD in smokers.

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Correspondence to Mona M. Fathy.

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Fathy, M.M., Youssif, O.A. & Ashour, W.M. The slow activity-associated genotype of microsomal epoxide hydroxylase-1 (m-EPHX-1) and low serum paraoxonase-1 (PON1) activity are associated with increased susceptibility to chronic obstructive pulmonary disease (COPD) in smokers. Comp Clin Pathol 22, 355–361 (2013). https://doi.org/10.1007/s00580-012-1416-7

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Keywords

  • COPD
  • Paraoxonase1
  • Microsomal epoxide hydrolase-1