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We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds(More)
OBJECTIVE The E23K variant in the Kir6.2 subunit of the ATP-sensitive K(+) channel (K(ATP) channel) is associated with increased risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms responsible. To avoid confounding effects of hyperglycemia, insulin secretion and action were studied in subjects with the(More)
PKClambda is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding(More)
Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1,(More)
Monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) secreted by adipocytes is a member of the CC chemokine family and plays a pivotal role in the inflammatory process. A polymorphism, the -2518 A/G of MCP-1 gene, has been associated with type 2 diabetes, type 1 diabetes, parameters of insulin resistance and obesity. Therefore, we investigated the(More)
MOTIVATION Preliminary results on the data produced using the Affymetrix large-scale genotyping platforms show that it is necessary to construct improved genotype calling algorithms. There is evidence that some of the existing algorithms lead to an increased error rate in heterozygous genotypes, and a disproportionately large rate of heterozygotes with(More)
Regulation of hepatic gene expression is important for energy homeostasis. We now show that hepatic expression of the gene for the transcription factor Kruppel-like factor 15 (KLF15) is increased by food deprivation and reduced by feeding in mice. Expression of the KLF15 gene in mouse liver was also down-regulated by a euglycemic-hyperinsulinemic clamp and(More)
Transcription factor 7-like 2 (TCF7L2) has been shown to be associated with type 2 diabetes mellitus in multiple ethnic groups. Regarding the Asian population, Horikoshi et al. (Diabetologia 50:747-751, 2007) and Hayashi et al. (Diabetologia 50:980-984, 2007) reported that single nucleotide polymorphisms (SNPs) in TCF7L2 were associated with type 2 diabetes(More)
Type 2 diabetes mellitus (T2DM) is a group of multifactorial disorders due to either defective insulin secretion or action. Despite the fact that numerous genetic researches of T2DM have been pursued, the pathogenic mechanisms remain obscure. We encountered a T2DM family associated with a balanced reciprocal translocation, t(3;9)(p21.31;q33.1). To isolate a(More)
BACKGROUND In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates. OBJECTIVE AND DESIGN The aim of this study was to replicate in a Japanese population previously(More)