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Glutathione-S-Transferase (GST) P1, GSTM1, Exercise, Ozone and Asthma Incidence in School Children
  1. Talat Islam (islam{at}usc.edu)
  1. University of Southern California, United States
    1. Kiros Berhane (kiros{at}usc.edu)
    1. University of Southern California, United States
      1. Rob McConnell (rmcconne{at}usc.edu)
      1. Department of Preventive Medicine, USC Keck School of Medicine, United States
        1. W James Gauderman (jimg{at}usc.edu)
        1. University of Southern California, United States
          1. Edward Avol (avol{at}usc.edu)
          1. University of Southern California, United States
            1. John M Peters (jpeters{at}usc.edu)
            1. University of Southern California, United States
              1. Frank D Gilliland (gillilan{at}usc.edu)
              1. University of Southern California, United States

                Abstract

                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 inter-related 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 ile105 homozygotes but not among those with at least one val105 allele (interaction p-value=0.02). Risk was highest among ile105 homozygotes who participated in ≥3 sports in the high-ozone communities (HR: 6.15, 95%CI 2.2-7.4). GSTM1 null was independently associated with increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth-grade cohorts recruited in 1993 and 1996.

                Conclusion: Children who inherit a val105 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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