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American Journal of Epidemiology Advance Access published online on November 6, 2009
American Journal of Epidemiology, doi:10.1093/aje/kwp310
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American Journal of Epidemiology © The Author 2009. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Functional Variants in the Catalase and Myeloperoxidase Genes, Ambient Air Pollution, and Respiratory-related School Absences: An Example of Epistasis in Gene-Environment Interactions

Madé Wenten, W. James Gauderman, Kiros Berhane, Pi-Chu Lin, John Peters and Frank D. Gilliland*

* Correspondence to Dr. Frank D. Gilliland, Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033 (e-mail: gillilan{at}hsc.usc.edu).

Received for publication February 17, 2009. Accepted for publication September 2, 2009.

The individual effect of functional single nucleotide polymorphisms within the catalase and myeloperoxidase genes (CAT and MPO) has been studied in relation to asthma; however, their interrelationship with ambient air pollution exposures has yet to be determined. The authors investigated the interrelationships between variants in CAT and MPO, ambient air pollutants, and acute respiratory illness. Health information, air pollution, and incident respiratory-related school absences were ascertained in January–June 1996 for 1,136 Hispanic and non-Hispanic white US elementary schoolchildren as part of the prospective Children's Health Study. Functional and tagging single nucleotide polymorphisms for the CAT and MPO loci were genotyped. The authors found epistasis between functional polymorphisms in the CAT/MPO loci, which differed by levels of oxidant-stress-producing air pollutants. Risk of respiratory-related school absences was elevated for children with the CAT (G/G) and MPO (G/A or A/A) genes (relative risk = 1.35, 95% confidence interval: 1.03, 1.77; P-interaction = 0.005). The epistatic effect of CAT and MPO variants was most evident in communities exhibiting high ambient ozone levels (P-interaction = 0.03). The association of respiratory-illness absences with functional variants in CAT and MPO that differ by air pollution levels illustrates the need to consider genetic epistasis in assessing gene-environment interactions.

air pollution; catalase; epistasis, genetic; peroxidase; respiratory tract infections

Abbreviations: CAT, catalase; MPO, myeloperoxidase; PM10, particulate matter less than 10 µm in aerodynamic diameter; SNP, single nucleotide polymorphism


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