Association study of the effect of WFS1 polymorphisms on risk of type 2 diabetes in Japanese population.
Mutations of WFS1 gene cause Wolfram syndrome, which is a rare autosomal recessive disorder characterized by juvenile diabetes mellitus, optic atrophy, deafness and diabetes insipidus. The product encoded by WFS1 gene, wolframin, could be involved in ER stress response causing beta-cell loss through impaired cell cycle progression and increased apoptosis. Recently, polymorphisms in the WFS1 gene were strongly associated with type 2 diabetes in Caucasians. The aim of the present study was to examine whether the variants of WFS1 are associated with risk of type 2 diabetes in Japanese individuals. Four single nucleotide polymorphisms, rs6446482, rs12511742, rs1801208 (R456H) and rs734312 (H611R) were genotyped in a total of 536 diabetic patients and 398 nondiabetic control subjects. Among the four variants, rs12511742 showed a marginal association with susceptibility to type 2 diabetes (odds ratio = 1.32, 95% confidence interval = 1.02-1.71, P = 0.033). Carriers of the risk allele at rs12511742 exhibited lower pancreas beta-cell function (P = 0.017). However, this association disappeared after adjustment for sex, age and BMI (Adjusted P = 0.24). Although we found no evidence for a substantial effect of WFS1 polymorphisms on risk of type 2 diabetes or clinical characteristics of diabetic subjects in Japanese population, this gene is still a good candidate for a type 2 diabetes susceptibility gene, potentially, through impaired insulin secretion.
Mita
Masaki
M
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Miyake
Kazuaki
K
Zenibayashi
Masako
M
Hirota
Yushi
Y
Teranishi
Tetsuya
T
Kouyama
Kunichi
K
Sakaguchi
Kazuhiko
K
Kasuga
Masato
M
D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D008565:Membrane Proteins; C114987:wolframin protein