doi: 10.1161/hq0701.092146
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Genetic Contributions to Plasma Total Antioxidant Activity
From the Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Tex, and the Department of Medicine (B.D.M.), University of Maryland, Baltimore.
Correspondence to Dr X.L. Wang, Department of Genetics, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227-5301. E-mail xwang{at}darwin.sfbr.org
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.
Key Words: antioxidants • coronary disease • genetics • statistics • smoking
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