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.
Hirai
Masashi
M
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. mhirai@int3.med.tohoku.ac.jp
Suzuki
Susumu
S
Hinokio
Yoshinori
Y
Yamada
Takahiro
T
Yoshizumi
Shinsuke
S
Suzuki
Chitose
C
Satoh
Jo
J
Oka
Yoshitomo
Y
D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001120:Arginine; D003545:Cysteine; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000517:prevention & control*; D005090:Exodeoxyribonucleases; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053484:RecQ Helicases; D017741:Survivors; D000071657:Werner Syndrome Helicase
D001120:Arginine; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D003545:Cysteine