Ozone, Oxidant Defense Genes, and Risk of Asthma during Adolescence
Year: 2007
Type: article
Study design: Observational Study
Abstract: 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 = 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. 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 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. 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.
Institution: University of Southern California
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Factors in Childhood Lung Susceptibility to Pollution, G2369551729, Genetics, Air Pollution, and Respiratory Effects in Children and Young Adults, G3112809935, G4243571177, Air Pollution, Inflammation and New Onset Asthma, G5802368188, G6731270986, G7817187309, Children's Environmental Health Center, Environmental Exposures, Host Factors and Human Disease
OpenAlex ID: W1967957095