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Am J Respir Crit Care Med. 2008 Feb 15;177(4):388-95. Epub 2007 Nov 29.

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

Author information

1
M.D. Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033, USA.

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.

PMID:
18048809
PMCID:
PMC2258440
DOI:
10.1164/rccm.200706-863OC
[Indexed for MEDLINE]
Free PMC Article

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