Polymorphisms for microsomal epoxide hydrolase and genetic susceptibility to COPD.
Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD, which suggests the presence of genetic susceptibility. The human microsomal epoxide hydrolase (EH) is a metabolizing enzyme which involves the process of numerous reactive epoxide intermediates and contains polymorphic alleles which are associated with altered EH activity and may be linked to increased risk for COPD. To determine whether the EH polymorphisms contributed to increased risk for COPD, prevalence of the EH codons 113 and 139 polymorphisms were compared between COPD patients and controls by a PCR-RFLP analysis using genomic DNA isolated from 131 COPD patients and 262 individually matched controls by age (+/-5 years) among Caucasians with 2:1 ratio. Significantly increased risk for COPD was observed for subjects with the EH(113His/His) genotypes (OR=2.4, 95% CI=1.1-5.1). These results were consistent with the fact that a significant trend towards increased risk was observed with predicted less protective EH codon 113 genotypes (p=0.03, trend test). A similar association was not observed for EH codon 139 polymorphism. As expected, a significant correlation between smoking dose and severity of COPD was observed (p<0.001). These results suggest that EH codon 113 polymorphism may modify risk for COPD.
Park
Jong Y
JY
Division of Cancer Prevention and Controls, Molecular Screening Section, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. parkj@moffitt.usf.edu
Chen
Lan
L
Wadhwa
Nina
N
Tockman
Melvyn S
MS
D000368:Aged; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D004851:Epoxide Hydrolases