Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema

CAD Smith, DJ Harrison - The Lancet, 1997 - thelancet.com
CAD Smith, DJ Harrison
The Lancet, 1997thelancet.com
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 …
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.
Findings
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.
Interpretation
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.
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