EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis

J. Lee, B.G. Nordestgaard, M. Dahl


We tested the hypothesis that two well-characterised functional polymorphisms of the microsomal epoxide hydrolase gene (EPHX1), T113C and A139G, may influence susceptibility to COPD and asthma.

We genotyped participants from the Copenhagen City Heart Study (n=10,038) and the Copenhagen General Population Study (n=37,022) for the T113C and A139G variants in the EPHX1 gene and measured lung function and recorded COPD hospitalisation and asthma and smoking history. Finally, we meta-analysed results from 19 studies including 7489 COPD cases and 42,970 controls.

The odds ratio for spirometry-defined COPD or COPD hospitalisation did not differ from 1.0 for any of the EPHX1 genotypes or phenotypes overall, or in smokers or nonsmokers separately (p for trend 0.18–0.91). Likewise, EPHX1 genotypes or phenotypes did not associate with risk of asthma (p for trend 0.46–0.98). In meta-analysis, random effects odds ratios for COPD in T113C heterozygotes and homozygotes vs. non-carriers were 1.17 (0.99–1.38) and 1.38 (1.09–1.74), respectively. Corresponding values for A139G were 0.93 (0.83–1.05) and 0,89 (0.78–1.02).

Our results indicate that genetically reduced microsomal epoxide hydrolase activity is not a major risk factor for COPD or asthma in the Danish population; however, meta-analysis cannot completely exclude a minor effect on COPD risk.