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


OBJECTIVE
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.


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.
M.D. Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033, USA.
Talat
T
Islam
Rob
R
McConnell
W James
WJ
Gauderman
Ed
E
Avol
John M
JM
Peters
Frank D
FD
Gilliland
D000293:Adolescent; D000393:Air Pollutants / Q000032:analysis; D000483:Alleles; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D004784:Environmental Monitoring; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D019570:Inhalation Exposure / Q000032:analysis / Q000517:prevention & control; D008297:Male; D018384:Oxidative Stress / Q000235:genetics; D010126:Ozone / Q000032:analysis; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D000393:Air Pollutants; D010126:Ozone; D002374:Catalase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase