Manganese superoxide dismutase Ala16Val polymorphism is associated with the development of type 2 diabetes in Japanese-Americans.
OBJECTIVE
Recent evidence indicates that oxidative stress may play an important role in the pathogenesis of insulin resistance and that gene polymorphism (Ala16Val) of manganese superoxide dismutase (MnSOD) may protect against reactive oxygen species (ROS) function. We aimed to test the hypothesis that the Ala16Val variant could be associated with the development of type 2 diabetes.


METHODS
We examined 523 nondiabetic Japanese-Americans who underwent a 75g oral glucose tolerance test (OGTT) and were followed for an average of 9.9 years. Cox proportional hazard analysis, stratified by category of OGTT, was used to determine whether the Ala16Val polymorphism was a risk factor in the development of type 2 diabetes.


RESULTS
During the follow-up period, 65 subjects developed type 2 diabetes. Compared with Ala allele carriers, subjects with a Val homozygote showed significantly higher risk for developing diabetes (stratified hazard ratio=2.05 [95% confidence interval 1.03-4.08]; P=0.041) after adjustment for age, gender, systolic blood pressure, total cholesterol, body mass index, and homeostasis model assessment.


CONCLUSIONS
We demonstrated that the MnSOD Ala16Val polymorphism might be associated with development of type 2 diabetes among Japanese-Americans. These results suggest that insufficient ROS scavenging might be associated with a susceptibility to glucose intolerance.
Nakanishi
S
S
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. n-shuhei@umin.net
Yamane
K
K
Ohishi
W
W
Nakashima
R
R
Yoneda
M
M
Nojima
H
H
Watanabe
H
H
Kohno
N
N
D000409:Alanine; D019943:Amino Acid Substitution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D014481:United States; D014633:Valine
D007328:Insulin; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014633:Valine; D000409:Alanine