Ozone, oxidant defense genes and risk of asthma during adolescence

Islam, T; Mcconnell, R; Gauderman, WJ; Avol, E; Peters, JM; Gilliland, FD

HERO ID

97348

Reference Type

Journal Article

Year

2008

Language

English

PMID

18048809

HERO ID 97348
In Press No
Year 2008
Title Ozone, oxidant defense genes and risk of asthma during adolescence
Authors Islam, T; Mcconnell, R; Gauderman, WJ; Avol, E; Peters, JM; Gilliland, FD
Journal American Journal of Respiratory and Critical Care Medicine
Volume 177
Issue 4
Page Numbers 388-395
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.
Doi 10.1164/rccm.200706-863OC
Pmid 18048809
Wosid WOS:000253222800007
Url https://www.atsjournals.org/doi/10.1164/rccm.200706-863OC
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science 000253222800007
Is Public Yes
Language Text English
Keyword Adolescent; Air Pollutants/analysis; Alleles; Asthma/ethnology/*genetics/metabolism; Catalase/*genetics/metabolism; Cohort Studies; Environmental Monitoring; Female; Gene Expression Regulation; Genotype; Heme Oxygenase-1/*genetics; Hispanic Americans/statistics & numerical data; Humans; Incidence; Inhalation Exposure/analysis/prevention & control; Male; Oxidative Stress/genetics; Ozone/analysis; *Polymorphism, Genetic; Prognosis; Risk Assessment; Severity of Illness Index; Superoxide Dismutase/*genetics/metabolism
Is Qa No
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