Background: Epidemiologic studies indicate that exposure to air pollution caused by traffic may have an association with an increased risk of childhood asthma. Some studies report an association between the polymorphisms of the microsomal epoxide hydroxylase (EPHX1) gene and enzyme activity. We investigated the associations of EPHX1 Tyr113His and His139Arg polymorphisms with asthma and wheezing outcomes, and focused on the functional genetic change in different ambient nitrogen dioxide (NO₂) levels on glutathione S-transferase p1 (GSTP1) and glutathione S-transferase m1 (GSTM1) genotypes.
Methods: A total of 3,741 children were enrolled in the Taiwan Children Health Study from 14 communities. We examined the associations of EPHX1 Tyr113His and His139Arg genotypes and diplotypes with asthma and wheezing outcomes under different ambient NO₂ exposures.
Results: Children with the EPHX1 Arg/His or Arg/Arg genotypes at codon 139 were significantly associated with increased risks of lifetime asthma (adjusted OR [aOR] = 1.3; 95% CI, 1.1-1.7; and aOR = 1.5; 95% CI, 1.1-2.1, respectively). The EPHX1 diplotypes showed significant associations with lifetime asthma (global P value = .01) and early-onset asthma (global P value = .01). The risk of EPHX1 139Arg allele and 113Tyr-139Arg diplotype were of greater magnitude in higher compared with lower NO₂ communities. The increase of the effect from the EPHX1 139Arg allele with higher NO₂ exposure was most marked in the GSTP1 Val allele and GSTM1 present genotype.
Conclusions: Children with high EPHX1 activity may have increase risk of asthma and wheezing outcomes, and can be mediated through airway oxidative stress generation.