Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Division of Environmental Health Sciences, School of Public Health, University of California-Berkeley, Berkeley, CA 94608, USA.
Maria
M
Bastaki
Karen
K
Huen
Paolo
P
Manzanillo
Neha
N
Chande
Connie
C
Chen
John R
JR
Balmes
Ira B
IB
Tager
Nina
N
Holland
D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People; D002374:Catalase / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005979:Glutathione Peroxidase / Q000097:blood*; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D011110:Polymorphism, Genetic; D012016:Reference Values; D013482:Superoxide Dismutase / Q000097:blood*; D044465:White People; D000094765:Glutathione Peroxidase GPX1
D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human