title: Genetic contributions to plasma total antioxidant activity.
abstract: Oxidative stress plays important roles in a wide spectrum of pathological processes, such as atherosclerosis. Although several environmental factors are documented to influence redox metabolism, relatively little is known about genetic effects. In the present study, we evaluated genetic contributions to variation in plasma total antioxidant status (TAS), a measure of peroxyl-scavenging capacity, in 1337 members of 40 Mexican American families. TAS levels were significantly lower in women than in men (1.675+/-0.004 versus 1.805+/-0.005 mmol/L, respectively; P<0.001), and there was a significant decline of TAS levels with age in men but not in women (P<0.01 for the interaction). Quantitative genetic analysis indicated the heritability of TAS levels to be 0.509+/-0.052; ie, approximately 51% of the residual variance (after covariate adjustment) in TAS levels was due to the additive effects of genes (P<0.001). We have further observed a significant gene-by-smoking interaction (P<0.05). Additive genetic effects account for 83% of the residual phenotypic variance in TAS levels among smokers, but they account for only 49% in nonsmokers. However, genes contributing to TAS variation are the same in smokers and nonsmokers. Our study for the first time demonstrates that TAS, an indicator of redox homeostasis, is under strong genetic control, especially among smokers. With appropriate tools, such as genome screening, it should be possible to localize genes that regulate redox homeostasis and, ultimately, identify the DNA sequence variants predisposing subjects to oxidative damage.
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78227-5301, USA. xwang@darwin.sfbr.org
authors.forename: X L
authors.initials: XL
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: J F
authors.initials: JF
authors.lastname: VandeBerg
authors.forename: B D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: M C
authors.initials: MC
authors.lastname: Mahaney
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D048909:Diabetes Complications; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
chemical_list: D017382:Reactive Oxygen Species