Ozone, oxidant defense genes, and risk of asthma during adolescence

Rationale: Although oxidative stress is a cardinal feature of asthma, the roles of oxidant air pollutants and antioxidant genes heme oxygenase 1 (HMOX-1), catalase (CAT), and manganese superoxide dismutase (MNSOD) in asthma pathogenesis have yet to be determined. Objectives: We hypothesized that the functional polymorphisms of HMOX-1 ([GT](n) repeat), CAT (-262C > T -844C > T), and MNSOD (Ala-9Val) are associated with new-onset asthma, and the effects of these variants vary by exposure to ozone, a potent oxidant air pollutant. Methods: We assessed this hypothesis in a population-based cohort of non-Hispanic (n = 11,1125) and Hispanic white (n = 586) children who resided in 12 California communities and who were followed annually for 8 years to ascertain new-onset asthma. Measurements and Main Results: Air pollutants were continuously measured in each of the study communities during the 8 years of study follow-up. HMOX-1 "short" alleles (< 23 repeats) were associated with a reduced risk for new-onset asthma among non-Hispanic whites (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.41-0.99). This protective effect was largest in children residing in low-ozone communities (HR, 0.48; 95% CI, 0.25-0.91) (interaction Pvalue = 0.003). Little evidence for an association with HMOX-1 was observed among Hispanic children. In contrast, Hispanic children with a variant of the CAT-262 "T" allele (CT or TT) had an increased risk for asthma (H R, 1.78; P value = 0.01). The effects of these polymorphisms were not modified by personal smoking or secondhand-smoke exposure. Conclusions: Functional promoter variants in CAT and HMOX-1 showed ethnicity-specific associations with new-onset asthma. Oxidant gene protection was restricted to children living in low-ozone communities.