title: Associations between catalase phenotype and genotype: modification by epidemiologic factors.
abstract: Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C --> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C --> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk.
authors.affiliation: Department of Epidemiology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.forename: Susan
authors.initials: S
authors.lastname: Nowell
authors.forename: Susan E
authors.initials: SE
authors.lastname: McCann
authors.forename: Jihnhee
authors.initials: J
authors.lastname: Yu
authors.forename: Lisa
authors.initials: L
authors.lastname: Carter
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Lang
authors.forename: Fred F
authors.initials: FF
authors.lastname: Kadlubar
authors.forename: Luke D
authors.initials: LD
authors.lastname: Ratnasinghe
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D015981:Epidemiologic Factors; D004910:Erythrocyte Membrane / Q000201:enzymology*; D005260:Female; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D044465:White People; D001741:Black or African American
chemical_list: D002374:Catalase