Airway oxidative stress is a cardinal feature and an important pathway in asthma pathogenesis.[1] Although a growing body of evidence supports a joint role for air pollutants and variants in genes involved in oxidant defenses in asthma pathogenesis,[2] (original) (raw)

Background: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesized that GSTP1, GSTM1, exercise and ozone exposure have interrelated effects on asthma pathogenesis. Methods: We examined associations of the well characterized null variant of GSTM1 and four SNPs that characterized common variation in the GSTP1 locus with new-onset asthma in a cohort of 1,610 school children. Children's exercise and ozone-exposure were classified using participation in team sports and community annual average ozone levels, respectively. Results: A two SNP model involving putatively functional variants (rs6591255, rs1695 [Ile105Val]) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (HR 0.60, 95% CI 0.4, 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95%CI 1.1-1.9). Asthma risk increased with level of exercise among ile 105 homo...