Title: Ozone, oxidant defense genes, and risk of asthma during adolescence.
Authors: Islam, Talat; McConnell, Rob; Gauderman, W James; Avol, Ed; Peters, John M; Gilliland, Frank D
Published In Am J Respir Crit Care Med, (2008 Feb 15)
Abstract: 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.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.We assessed this hypothesis in a population-based cohort of non-Hispanic (n = 1,125) 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.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 P value = 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 (HR, 1.78; P value = 0.01). The effects of these polymorphisms were not modified by personal smoking or secondhand-smoke exposure.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.
PubMed ID: 18048809
MeSH Terms: Adolescent; Air Pollutants/analysis; Alleles; Asthma/ethnology; Asthma/genetics*; Asthma/metabolism; Catalase/genetics*; Catalase/metabolism; Cohort Studies; Environmental Monitoring; Female; Gene Expression Regulation; Genotype; Heme Oxygenase-1/genetics*; Hispanic Americans/statistics & numerical data; Humans; Incidence; Inhalation Exposure/analysis; Inhalation Exposure/prevention & control; Male; Oxidative Stress/genetics; Ozone/analysis; Polymorphism, Genetic*; Prognosis; Risk Assessment; Severity of Illness Index; Superoxide Dismutase/genetics*; Superoxide Dismutase/metabolism