Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children (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 GSTP1 with new-onset asthma in a cohort of 1,610 school children. Children's exercise and ozone-exposure status were classified using participation in team sports and community-specific ozone levels, respectively. Results-A two SNP model (rs6591255, rs1695 [Ile105Val]) best captured the association between GSTP1 and asthma. Compared to children with common alleles for both the SNPs, 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 homozygotes but not among those with at least one val 105 allele (interaction p-value=0.02). Risk was highest among ile 105 homozygotes who participated in ≥3 sports in the highozone communities (HR: 6.15, 95%CI: 2.2-7.4). GSTM1 null was independently associated with asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth-grade cohorts in the study population recruited in 1993 and 1996. Conclusion-Children who inherit a val 105 variant allele may be protected from the increased risk of asthma associated with exercise, especially in high-ozone communities. GSTM1 null genotype was associated with increased risk of asthma.
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