October 2011, VOLUME128 /ISSUE Supplement 3

Microsomal Epoxide Hydroxylase Genotypes/Diplotypes, Traffic Air Pollution, and Childhood Asthma

KY Tung, CH Tsai, YL Lee. Chest. 2011;139(4):839848
  1. Melinda M. Rathkopf, MD
  1. Anchorage, AK


The gene that encodes microsomal epoxide hydroxylase, (EPHX1, is responsible for detoxification of reactive epoxides to generate reactive oxygen species. The different polymorphisms influence EPHX1 activity. The associations of EPHX1 Tyr113His and His139Arg genotypes and diplotypes with asthma and wheezing outcomes were examined with a focus on the functional genetic change in glutathione S-transferase m1 (GSTM1) genotypes.


The study included 3741 7th-grade schoolchildren from 14 communities enrolled in the Taiwan Children Health Study.


Asthma and wheeze status was determined by a baseline questionnaire. Children were classified as having lifetime asthma (physician-diagnosed asthma) or early-onset asthma (onset at <5 years old). Air pollution data (average hourly NO2 level) were available from monitoring stations for the Taiwan Environmental Protection Agency. DNA was collected from oral mucosa, and genomic DNA was isolated.


Having the EPHX1 Arg/His or Arg/Arg genotypes at codon 139 was significantly associated with increased risks of lifetime asthma (adjusted odds ratio [aOR]: 1.3 [95% confidence interval (CI): 1.1–1.7] and 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 113Tyr139Arg diplotype was of greater magnitude in higher-NO2 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.


Children with high EPHX1 activity have an increased risk of asthma and wheezing outcomes. The risk is higher with high NO2 exposure and a GSTP1 105Val allele or GSTM1-present genotype, which suggests that these common genetic polymorphisms and diplotypes play important roles in asthma pathogenesis among children, depending on airway oxidative stress.


This article, although technical, sheds light on the scientific background of a basic premise in asthma: the association of air pollution on asthma risk. The results of previous studies have suggested that exposure to air pollution carries an increased risk of asthma. This study examined the genetic basis of this principle with a focus on the epoxide hydroxylase enzyme activity. An increased risk of asthma was seen in children with certain genotypes, and the risk was of higher magnitude depending on environmental NO2 levels. These results add to the complex pathogenesis of asthma in regards to both genetic and environmental influences.