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Thorax 62:1050-1057 doi:10.1136/thx.2007.080127
  • Asthma

Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma

  1. Muhammad T Salam,
  2. Pi-Chu Lin,
  3. Edward L Avol,
  4. W James Gauderman,
  5. Frank D Gilliland
  1. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA
  1. Dr Frank D Gilliland, Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, California 90033, USA; gillilan{at}usc.edu
  • Received 21 February 2007
  • Accepted 2 July 2007
  • Published Online First 21 August 2007

Abstract

Background: Microsomal epoxide hydrolase (EPHX1) metabolises xenobiotics including polyaromatic hydrocarbons (PAHs). Functional variants at this locus have been associated with respiratory diseases. The effects of EPHX1 variants may depend upon exposures from tobacco smoke and traffic emissions that contain PAHs as well as variants in other enzymes in the PAH metabolic pathway such as glutathione S-transferase (GST) genes. A study was undertaken to investigate associations of variants in EPHX1, GSTM1, GSTP1 and GSTT1 with asthma and the relationships between asthma, EPHX1 metabolic phenotypes and exposure to sources of PAHs.

Methods: Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate the associations of genetic variants and exposures with asthma phenotypes using data from 3124 children from the Children’s Health Study.

Results: High EPHX1 activity was associated with an increased risk for lifetime asthma (OR 1.51, 95% CI 1.14 to 1.98) which varied by GSTP1 Ile105Val genotype and by residential proximity to major roads (p for interaction = 0.006 and 0.03, respectively). Among children with GSTP1 105Val/Val genotype, those who had high EPHX1 phenotype had a fourfold (95% CI 1.97 to 8.16) increased risk of lifetime asthma than children with low/intermediate EPHX1 phenotype. Among children living within 75 metres of a major road, those with high EPHX1 activity had a 3.2-fold (95% CI 1.75 to 6.00) higher lifetime asthma risk than those with low/intermediate activity. The results were similar for current, early persistent and late onset asthma. Children with high EPHX1 phenotype, GSTP1 Val/Val genotype who lived <75 metres from a major road were at the highest asthma risk.

Conclusion: EPHX1 and GSTP1 variants contribute to the occurrence of childhood asthma and increase asthma susceptibility to exposures from major roads.

Footnotes

  • This study was supported by the National Institute of Environmental Health Sciences (grants 5P01 ES09581, 5P01ES011627 and 5P30 ES07048), the US Environmental Protection Agency (grants R826708-01 and RD83186101), the National Heart, Lung, and Blood Institute (grants 5R01HL61768 and 5R01HL076647), the California Air Resources Board (contract 94-331) and the Hastings Foundation. The study sponsors had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the paper for publication.

  • Competing interests: None.

  • Abbreviations:
    AKR1
    aldo-keto reductase family 1
    EPHX1
    epoxide hydrolase
    GST
    glutathione S-transferase
    PAH
    polyaromatic hydrocarbon
    ROS
    reactive oxygen species
    SNP
    single nucleotide polymorphism