title: Functional variants in the catalase and myeloperoxidase genes, ambient air pollution, and respiratory-related school absences: an example of epistasis in gene-environment interactions.
abstract: 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.
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Madé
authors.initials: M
authors.lastname: Wenten
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.forename: Kiros
authors.initials: K
authors.lastname: Berhane
authors.forename: Pi-Chu
authors.initials: PC
authors.lastname: Lin
authors.forename: John
authors.initials: J
authors.lastname: Peters
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gilliland
mesh_terms: D000041:Absenteeism; D000208:Acute Disease; D000393:Air Pollutants / Q000633:toxicity*; D002374:Catalase / Q000235:genetics*; D002648:Child; D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino; D006801:Humans; D009585:Nitrogen Dioxide / Q000633:toxicity; D010126:Ozone / Q000633:toxicity; D052638:Particulate Matter / Q000633:toxicity; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012140:Respiratory Tract Diseases / Q000453:epidemiology* / Q000235:genetics; D012574:Schools; D044465:White People
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D010126:Ozone; D002374:Catalase; D009195:Peroxidase; D009585:Nitrogen Dioxide