Showing papers by "Kazuo Hara published in 2008"

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

Abstract: We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).

Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects.

Abstract: 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 in the Japanese population, while contradictory results were reported for Han Chinese populations. The aim of this study was to investigate the associations of the TCF7L2 gene with type 2 diabetes using a relatively large sample size: 2,214 Japanese individuals with type 2 diabetes and 1,873 normal controls. The minor alleles of rs7903146, rs11196205, and rs12255372 showed significant associations with type 2 diabetes (OR=1.48, P=2.7 x 10(-4); OR=1.39, P=4.6 x 10(-4); OR=1.70, P=9.8 x 10(-5), respectively) in the combined sample sets. However, neither rs11196218 nor rs290487 showed a significant association. These results indicate that TCF7L2 is an important susceptibility gene for type 2 diabetes in the Japanese population.

Endoscopic ultrasound‐guided ethanol injection in the pancreas in a porcine model: A preliminary study

Abstract: Background and Aim: Despite aggressive multimodal treatments, survival rates for patients with pancreatic cancer remain disappointing. Local progression is problematic, and minimally invasive procedures allowing locoregional control are needed. In this study, we attempted endoscopic ultrasound (EUS)-guided injection of ethanol into the pancreas. Methods: Under EUS guidance, pure ethanol (2 mL) was injected into normal tissue of the pancreatic body in two anesthetized domestic pigs. Serum concentrations of amylase, aspartame aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured before treatment and at 2 h, 48 h and 2 weeks after injection. Body weight and clinical signs were also observed. After the animals were euthanized, the pancreases were analyzed histologically. Results: EUS imaging allows real-time surveillance of the injection procedure. Mild diarrhea was noted in one animal, but no other adverse effects were observed. No marked changes in laboratory tests were noted. Histologically, parenchymal necrosis extending over a wide area was seen without severe inflammation. Conclusion: EUS-guided ethanol injection in the pancreas seems to be technically simple. More detailed assessments of the safety and dose–effect relationship issues associated with this procedure are required.

Genetic Variations of Mrf-2/Arid5b Confer Risk of Coronary Atherosclerosis in the Japanese Population

Abstract: A phenotypic change of smooth muscle cells (SMCs) is considered to be critical in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD). Mrf-2/ARID5B, a member of the AT-rich interaction domain family of transcription factors, is highly expressed in the cardiovascular system and is believed to play essential roles in the phenotypic change of SMCs through its regulation of SMC differentiation. In addition, recent studies on gene-engineered mice suggested that this transcriptional factor is involved in obesity and adipogenesis, which are critical aspects for the pathogenesis of atherosclerosis. Thus, we hypothesized that genetic variations of the Mrf-2 gene might be associated with susceptibility to CAD. We investigated 11 common genetic variations of Mrf-2 to determine whether they were associated with susceptibility to CAD in 475 CAD subjects and 310 control subjects. The prevalence of homozygotes for the minor allele G of SNP4 (rs2893880) and minor allele G of SNP6 (rs7087507) were significantly more frequent in the control subjects than in patients with CAD (P = 0.0002, rs2893880, P = 0.0058, rs7087507). Four nearby SNPs (SNP4 to SNP7) (rs2893880, rs10740055, rs7087507 and rs10761600) showed almost complete linkage disequilibrium, and haplotype analysis revealed that the haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was also significantly negatively associated with susceptibility to CAD (P = 0.049). Moreover, these negative disease associations still existed after logistic regression analysis was taken into account to eliminate confounding conventional coronary risk factors. The results implicate possible disease relevance of the polymorphisms in the Mrf-2 gene with susceptibility to CAD. However, a larger scale prospective study is needed to clarify these findings.