Hirai Masashi, Suzuki Susumu, Hinokio Yoshinori, Yamada Takahiro, Yoshizumi Shinsuke, Suzuki Chitose, Satoh Jo, Oka Yoshitomo
Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Diabetes Res Clin Pract. 2005 Sep;69(3):287-92. doi: 10.1016/j.diabres.2005.01.012. Epub 2005 Mar 16.
Werner's syndrome is an autosomal recessive disease caused by mutation of the WRN gene, which may lead to DNA repair failure and acceleration of aging. A polymorphism at amino acid 1367 Cys (TTG)/Arg (CTG) reportedly reduces the risk of myocardial infarction in Japanese. We studied the possible involvement of this polymorphism in type 2 diabetes. When polymorphism of the WRN gene was analyzed in 272 randomly recruited type 2 diabetic subjects (age 64.5+/-11.1), we found those with Cys/Arg to be older than those with Cys/Cys (p=0.021) and that the age at diagnosis of diabetes was greater in Cys/Arg than in Cys/Cys subjects (p=0.011). Diabetes-free survival rate over the age, analyzed by Kaplan-Meier method, differed significantly between these two genotype groups (p=0.0125) and the survival curve was shifted to the right in the Cys/Arg group as compared to the Cys/Cys group. No difference in allele frequency was observed between our diabetic (n=272) and non-diabetic subjects (n=171, age 66.0+/-8.0). These results suggest that the 1367 Arg allele of the WRN gene protects against the development of type 2 diabetes mellitus in Japanese.
沃纳综合征是一种由WRN基因突变引起的常染色体隐性疾病，该突变可能导致DNA修复功能障碍并加速衰老。据报道，第1367位氨基酸处的半胱氨酸（TTG）/精氨酸（CTG）多态性可降低日本人患心肌梗死的风险。我们研究了这种多态性与2型糖尿病的可能关联。在随机招募到的272名2型糖尿病患者（年龄64.5±11.1岁）中分析WRN基因的多态性时，我们发现携带半胱氨酸/精氨酸的患者比携带半胱氨酸/半胱氨酸的患者年龄更大（p = 0.021），且半胱氨酸/精氨酸型患者的糖尿病诊断年龄大于半胱氨酸/半胱氨酸型患者（p = 0.011）。采用Kaplan-Meier法分析不同年龄组的无糖尿病生存率，这两种基因型组之间存在显著差异（p = 0.0125），与半胱氨酸/半胱氨酸组相比，半胱氨酸/精氨酸组的生存曲线向右偏移。在我们的糖尿病患者（n = 272）和非糖尿病患者（n = 171，年龄66.0±8.0岁）之间未观察到等位基因频率的差异。这些结果表明，WRN基因的1367精氨酸等位基因可预防日本人患2型糖尿病。
