Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema.
BACKGROUND
The first-pass metabolism of foreign compounds in the lung is an important protective mechanism against oxidative stress. We investigated whether polymorphisms in the gene for microsomal epoxide hydrolase (mEPHX), an enzyme involved in this protective process, had any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease (COPD) and emphysema.


METHODS
We designed PCR-based genotyping assays to detect variant forms of mEPHX that confer slow and fast activity. We used these assays to screen 203 blood-donor controls and groups of patients with asthma (n = 57), lung cancer (n = 50), COPD (n = 68), and emphysema (n = 94), who were attending specialised clinics in Edinburgh, UK.


RESULTS
The proportion of individuals with innate slow mEPHX activity (homozygotes) was significantly higher in both the COPD group and the emphysema group than in the control group (COPD 13 [19%] vs control 13 [6%]; emphysema 21 [22%] vs 13 [6%]). The odds ratios for homozygous slow activity versus all other phenotypes were 4.1 (95% CI 1.8-9.7) for COPD and 5.0 (2.3-10.9) for emphysema.


CONCLUSIONS
Genetic polymorphisms in xenobiotic enzymes may have a role in individual susceptibility to oxidant-related lung disease. Epoxide derivatives of cigarette-smoke components may be the cause of some of the lung damage characteristic of these diseases.
Smith
C A
CA
Department of Pathology, University of Edinburgh, UK.
Harrison
D J
DJ
D000328:Adult; D004198:Disease Susceptibility; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic
D004851:Epoxide Hydrolases