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 autosomalrecessive disorder characterized by juvenile diabetes mellitus, optic atrophy, deafnessand diabetes insipidus. The product encoded by WFS1 gene, wolframin, could beinvolved in ER stress response causing β-cell loss through impaired cell cycleprogression and increased apoptosis. Recently, polymorphisms in the WFS1 gene werestrongly associated with type 2 diabetes in Caucasians. The aim of the present studywas to examine whether the variants of WFS1 are associated with risk of type 2diabetes in Japanese individuals. Four single nucleotide polymorphisms, rs6446482,rs12511742, rs1801208 (R456H) and rs734312 (H611R) were genotyped in a total of 536diabetic patients and 398 nondiabetic control subjects. Among the four variants,rs12511742 showed a marginal association with susceptibility to type 2 diabetes (oddsratio = 1.32, 95% confidence interval = 1.02-1.71, P = 0.033). Carriers of the risk alleleat rs12511742 exhibited lower pancreas β-cell function (P = 0.017). However, thisassociation 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 riskof 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

Association of Serum MCP-1 Concentration and MCP-1 Polymorphism with Insulin Resistance in Japanese Individuals with Obese type 2 Diabetes

Monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) secreted byadipocytes is a member of the CC chemokine family and plays a pivotal role in theinflammatory process. A polymorphism, the -2518 A/G of MCP-1 gene, has beenassociated with type 2 diabetes, type 1 diabetes, parameters of insulin resistance andobesity. Therefore, we investigated the effects of MCP-1 single nucleotidepolymorphisms (SNPs) on the susceptibility to type 2 diabetes or insulin resistance inthe Japanese population. We also assessed the correlation between serum MCP-1concentration and other clinical characteristics in Japanese type 2 diabetic subjects.The serum MCP-1 concentration was significantly correlated with HOMA-IR and thevisceral fat area, but not with BMI. Although there was no association between thisSNP and type 2 diabetes, the -2518A/G polymorphism was associated with the serumMCP-1 concentration. In subgroup analysis, Japanese obese diabetic -2518AA carriershad a higher MCP-1 concentration and increased insulin resistance than obese diabetic-2518G carriers. These data indicated that the MCP-1 polymorphism was associatedwith insulin resistance in Japanese obese diabetic subjects and that MCP-1 wasimplicated in the pathogenesis of insulin resistance, especially associated with obesity,in humans