Nakanishi S, Yamane K, Ohishi W, Nakashima R, Yoneda M, Nojima H, Watanabe H, Kohno N
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Diabetes Res Clin Pract. 2008 Sep;81(3):381-5. doi: 10.1016/j.diabres.2008.06.003. Epub 2008 Jul 23.
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.
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.
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.
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.
最近的证据表明，氧化应激可能在胰岛素抵抗的发病机制中起重要作用，并且锰超氧化物歧化酶（MnSOD）的基因多态性（Ala16Val）可能对活性氧（ROS）功能具有保护作用。我们旨在检验Ala16Val变异体可能与2型糖尿病的发生有关这一假设。
我们对523名接受75克口服葡萄糖耐量试验（OGTT）且平均随访9.9年的非糖尿病日裔美国人进行了研究。采用按OGTT类别分层的Cox比例风险分析来确定Ala16Val多态性是否是2型糖尿病发生的危险因素。
在随访期间，65名受试者患上了2型糖尿病。在对年龄、性别、收缩压、总胆固醇、体重指数和稳态模型评估进行调整后，与Ala等位基因携带者相比，Val纯合子受试者患糖尿病的风险显著更高（分层风险比=2.05[95%置信区间1.03 - 4.08]；P = 0.041）。
我们证明了MnSOD Ala16Val多态性可能与日裔美国人中2型糖尿病的发生有关。这些结果表明，ROS清除不足可能与葡萄糖不耐受的易感性有关。
