Genetic contributions to plasma total antioxidant activity

Xing Li Wang, David L. Rainwater, Jane F. VandeBerg, Braxton D. Mitchell, Michael C. Mahaney

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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, ≅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.

Original languageEnglish (US)
Pages (from-to)1190-1195
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume21
Issue number7
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Antioxidants
  • Coronary disease
  • Genetics
  • Smoking
  • Statistics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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