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This study examined the association between genetic polymorphisms and enzyme activity for antioxidant enzymes that share a common detoxification pathway: manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1) and catalase.MnSOD, GPX1, and catalase activities were measured in isolated erythrocytes of 231 healthy, non-smoking student volunteers (55% women, ages 17–21, majority Asian or Caucasian). DNA from blood clots was genotyped by Taqman PCR (C47T : MnSOD and C593T : GPX1) and standard PCR (−262C>T : catalase). Associations between genotype and enzyme activity were analyzed by multiple linear regression, adjusted for baseline factors including gender and ethnicity.Minor allele frequencies ranged from 13% for catalase (T) to 18% for GPX1 (T), and 33% for MnSOD(C) with significant variation between ethnicities. Median GPX1 activity was 13.2 U/g Hb with a six-fold difference between lowest and highest levels. Catalase activity ranged eight-fold (median: 86.3 k/g Hb), while median MnSOD activity was 2.8 U/mg Hb with a 56-fold range of values. MnSOD enzyme activity was 15% higher in females than males (95%CI : −1%, 32%), and 33% higher in CT or TT individuals (C47T) versus CC individuals (95%CI : 7–59%). On average, catalase activity was 18.1 k/g Hb lower for TT subjects (−262C>T) versus CC subjects (95% CI: −32.3, −4.0). All enzyme activities were correlated (r=0.3–0.4, P<0.001).Interindividual variability of antioxidant enzyme activity in healthy young adults was partially explained by significant associations with three known genetic polymorphisms, and was further modified by gender and ethnicity. A substantial component of this variability may be attributable to differences in diet, environmental exposures, and additional genetic factors.