WRN gene 1367 Arg allele protects against development of type 2 diabetes mellitus

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.