論文 - 広瀬　寛

Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

Imamura Minako, Takahashi Atsushi, Yamauchi Toshimasa, Hara Kazuo, Yasuda Kazuki, Grarup Niels, Zhao Wei, Wang Xu, Huerta-Chagoya Alicia, Hu Cheng, Moon Sanghoon, Long Jirong, Kwak Soo Heon, Rasheed Asif, Saxena Richa, Ma Ronald C. W., Okada Yukinori, Iwata Minoru, Hosoe Jun, Shojima Nobuhiro, Iwasaki Minaka, Fujita Hayato, Suzuki Ken, Danesh John, Jorgensen Torben, Jorgensen Marit E., Witte Daniel R., Brandslund Ivan, Christensen Cramer, Hansen Torben, Mercader Josep M., Flannick Jason, Moreno-Macias Hortensia, Burtt Noel P., Zhang Rong, Kim Young Jin, Zheng Wei, Singh Jai Rup, Tam Claudia H. T., Hirose Hiroshi, Maegawa Hiroshi, Ito Chikako, Kaku Kohei, Watada Hirotaka, Tanaka Yasushi, Tobe Kazuyuki, Kawamori Ryuzo, Kubo Michiaki, Cho Yoon Shin, Chan Juliana C. N., Sanghera Dharambir, Frossard Philippe, Park Kyong Soo, Shu Xiao-Ou, Kim Bong-Jo, Florez Jose C., Tusie-Luna Teresa, Jia Weiping, Tai E. Shyong, Pedersen Oluf, Saleheen Danish, Maeda Shiro, Kadowaki Takashi

NATURE COMMUNICATIONS 7 2016年01月

ISSN  2041-1723

　概要を見る

<p>Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P-8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P</p>

• Access to Document (DOI)

Vitamin D deficiency with high intact PTH levels is more common in younger than in older women

Miyamoto Takeshi, Katsuyama Eri, Kanagawa Hiroya, Fujie Atsuhiro, Miyamoto Hiroya, Yoshida Shigeyuki, Mori Tomoaki, Miyamoto Kana, Sato Yuiko, Kobayashi Tami, Nakamura Masaya, Matsumoto Morio, Nishiwaki Yuji, Hirose Hiroshi, Kanda Takeshi, Saito Ikuo, Toyama Yoshiaki

Keio Journal of Medicine 65 （ 2 ） 33 - 38 2016年

ISSN  0022-9717

　概要を見る

<p>Low serum 25-hydroxyvitamin D (25(OH)D) levels are implicated as a risk factor for hip and spine fractures. Studies of the relation between 25(OH)D levels and fractures have primarily involved elderly osteoporosis patients or patients with fractures; however, the serum 25(OH)D and parathyroid hormone (PTH) status in younger adult populations remains largely unknown. We evaluated serum 25(OH)D and intact PTH levels in 411 women aged 39–64 years who were not receiving medication for osteoporosis or other bone diseases. Serum 25(OH)D levels were positively correlated with age (P = 0.019), whereas intact PTH levels were inversely correlated with 25(OH)D levels (P &lt;0.001). Thus, low vitamin D levels with high intact PTH levels were more common in younger than in older women. Our data show that serum 25(OH)D insufficiency could be a more serious concern in the younger population than had been previously anticipated. Because serum 25(OH)D insufficiency is reportedly a risk factor for hip and spine fracture, the number of fracture patients could increase in the future, suggesting that we may need to correct the serum vitamin D/intact PTH status to prevent future osteoporosis.</p>

• Access to Document (DOI)

Replication study of the association of rs7578597 in THADA, rs10886471 in GRK5, and rs7403531 in RASGRP1 with susceptibility to type 2 diabetes among a Japanese population

Sakai Kensuke, Imamura Minako, Tanaka Yasushi, Iwata Minoru, Hirose Hiroshi, Kaku Kohei, Maegawa Hiroshi, Watada Hirotaka, Tobe Kazuyuki, Kashiwagi Atsunori, Kawamori Ryuzo, Maeda Shiro

DIABETOLOGY INTERNATIONAL 6 （ 4 ） 306 - 312 2015年12月

ISSN  2190-1678

　概要を見る

<p>Aims: To evaluate the association of rs7578597 in THADA, rs10886471 in GRK5, rs7403531 in RASGRP1, and rs6723108 in TMEM163 with type 2 diabetes among the Japanese we performed a replication study of the association of these single nucleotide polymorphism (SNP) loci. Methods: We genotyped these 4 SNPs for 10,287 Japanese participants (7,478 type 2 diabetes, 2,809 controls) and used logistic regression analysis to examine the association of these SNPs with type 2 diabetes. Results: Rs6723108 was not polymorphic in our control group, and was excluded from the analysis. Rs7578597 was nominally associated with type 2 diabetes (p = 0.0186, odds ratio = 0.55, 95 % confidence interval = 0.33–0.90 adjusted for age, sex, and body mass index); however this association was not significant after Bonferroni correction (p ≥ 0.0125) and the effect direction was not consistent with that in the original report. There was significant heterogeneity in the allele frequency of rs7578597 among our control groups, and the nominal association was no longer observed (p = 0.58) after excluding a control collection in which the risk allele frequency was significantly higher than those in the other control collections. The remaining 2 SNP loci were not associated with type 2 diabetes in this Japanese population (p ≥ 0.05). We did not observe a significant association between the 3 SNPs and glycemic traits. Conclusions: The 4 loci have no significant effect on susceptibility to type 2 diabetes among the Japanese, although further evaluation with larger cohorts is necessary, especially for rs7578597 in THADA.</p>

• Access to Document (DOI)

Aging, Smoking, Dyslipidemia, and Obesity Are Independently Associated With the Prevalence of Colorectal Neoplasia in Japan: Analyses of Comprehensive Health Checkup Data

Inoue Nagamu, Takayama Michiyo, Makino Kanako, Matsuzaki Juntaro, Shiomi Eisuke, Shimizu Ryoko, Yoshida Toshifumi, Kashiwagi Kazuhiro, Hirose Hiroshi, Momoshima Suketaka, Sugino Yoshinori, Iwao Yasushi

AMERICAN JOURNAL OF GASTROENTEROLOGY 110   S601 - S601 2015年10月

ISSN  0002-9270

• Access to Document (DOI)

Palmitic acid-rich diet suppresses glucose-stimulated insulin secretion (GSIS) and induces endoplasmic reticulum (ER) stress in pancreatic islets in mice

Hirata Takumi, Kawai Toshihide, Hirose Hiroshi, Tanaka Kumiko, Kurosawa Hideaki, Fujii Chikako, Fujita Haruhisa, Seto Yoshiko, Matsumoto Hideo, Itoh Hiroshi

ENDOCRINE RESEARCH 41 （ 1 ） 8 - 15 2015年07月

ISSN  0743-5800

　概要を見る

<p>The objective was to clarify whether dietary palmitic acid supplementation affects glucose-stimulated insulin secretion (GSIS) and the endoplasmic reticulum (ER) stress pathway in pancreatic islets in mice. Eight-week-old male C57BL/6J mice were randomly divided into three treatment diet groups: control diet, palmitic acid-supplemented diet (PAL) and oleic acid-supplemented diet (OLE). After 2 weeks of treatment, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were performed. GSIS was assessed by pancreatic perfusion in situ with basal (100 mg/dL) glucose followed by a high (300 mg/dL) glucose concentration. We measured mRNA levels of ER stress markers such as C/EBP homologous protein (CHOP), immunoglobulin heavy-chain binding protein (BIP) and X-box binding protein (XBP)-1 using real-time polymerase chain reaction (PCR) analyses in isolated islets. Immunohistochemical staining was also performed. Mice fed PAL showed significantly decreased glucose tolerance (p &lt; 0.05). In the perfusion study, GSIS was significantly suppressed in the PAL group (p &lt; 0.05). Semi-quantitative RT-PCR revealed that islet CHOP, BIP, and XBP-1 mRNA expression were significantly increased in the PAL group (p &lt; 0.05). TUNEL-positive β-cells were not detected in all groups. Dietary palmitic acid-supplementation for 2 weeks might suppress GSIS and induce ER stress in pancreatic islets in mice, in the early stage of lipotoxicity.</p>

• Access to Document (DOI)

A Meta-analysis of Japanese Genome-Wide Association Studies Identified Seven Novel Susceptibility Loci to Type 2 Diabetes

Imamura Minako, Maeda Shiro, Yamauchi Toshimasa, Hara Kazuo, Takahashi Atsushi, Kubo Michiaki, Iwata Minoru, Hirose Hiroshi, Yasuda Kazuki, Watada Hirotaka, Maegawa Hiroshi, Ito Chikako, Tanaka Yasushi, Tobe Kazuyuki, Kaku Kohei, Kawamori Ryuzo, Kadowaki Takashi

DIABETES 64   A6 - A6 2015年06月

ISSN  0012-1797

Replication Study in a Japanese Population to Evaluate the Association between 10 SNP Loci, Identified in European Genome-Wide Association Studies, and Type 2 Diabetes

Matsuba Ren, Sakai Kensuke, Imamura Minako, Tanaka Yasushi, Iwata Minoru, Hirose Hiroshi, Kaku Kohei, Maegawa Hiroshi, Watada Hirotaka, Tobe Kazuyuki, Kashiwagi Atsunori, Kawamori Ryuzo, Maeda Shiro

PLOS ONE 10 （ 5 ）  2015年05月

ISSN  1932-6203

　概要を見る

<p>Aim: We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and 7 susceptibility loci originally identified by European genomewide association study (GWAS) in 2012: ZMIZ1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, and BCAR1. We also examined the association of 3 additional loci: CCND2 and GIPR, identified in sex-differentiated analyses, and LAMA1, which was shown to be associated with non-obese European type 2 diabetes. Methods: We genotyped 6,972 Japanese participants (4,280 type 2 diabetes patients and 2,692 controls) for each of the 10 single nucleotide polymorphisms (SNPs): rs12571751 in ZMIZ1, rs10842994 near KLHDC5, rs2796441 near TLE1, rs459193 near ANKRD55, rs10401969 in CILP2, rs12970134 near MC4R, rs7202877 near BCAR1, rs11063069 near CCND2, rs8108269 near GIPR, and rs8090011 in LAMA1 using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using a logistic regression analysis. Results: All SNPs examined in this study had the same direction of effect (odds ratio &gt; 1.0, p = 9.77 × 10&lt;sup&gt;-4&lt;/sup&gt;, binomial test), as in the original reports. Among them, rs12571751 in ZMIZ1 was significantly associated with type 2 diabetes [p = 0.0041, odds ratio = 1.123, 95% confidence interval 1.037-1.215, adjusted for sex, age and body mass index (BMI)], but we did not observe significant association of the remaining 9 SNP loci with type 2 diabetes in the present Japanese population (p ≥ 0.005). A genetic risk score, constructed from the sum of risk alleles for the 7 SNP loci identified by un-stratified analyses in the European GWAS meta-analysis were associated with type 2 diabetes in the present Japanese population (p = 2.3 × 10 &lt;sup&gt;-4&lt;/sup&gt;, adjusted for sex, age and BMI). Conclusions: ZMIZ1 locus has a significant effect on conferring susceptibility to type 2 diabetes also in the Japanese population.</p>

• Access to Document (DOI)

Effects of Oral Propranolol on a Juxtapapillary Capillary Hemangioma: A Single-Subject Pilot Study

Tanabe, H; Sahashi, K; Kitano, T; Tomita, Y; Saito, AM; Hirose, H

OPHTHALMIC SURGERY LASERS & IMAGING RETINA 46 （ 3 ） 380 - 383 2015年03月

ISSN  2325-8160

• Access to Document (DOI)

Genome-wide association study identifies three novel loci for type 2 diabetes

Hara Kazuo, Fujita Hayato, Johnson Todd A., Yamauchi Toshimasa, Yasuda Kazuki, Horikoshi Momoko, Peng Chen, Hu Cheng, Ma Ronald C. W., Imamura Minako, Iwata Minoru, Tsunoda Tatsuhiko, Morizono Takashi, Shojima Nobuhiro, So Wing Yee, Leung Ting Fan, Kwan Patrick, Zhang Rong, Wang Jie, Yu Weihui, Maegawa Hiroshi, Hirose Hiroshi, Kaku Kohei, Ito Chikako, Watada Hirotaka, Tanaka Yasushi, Tobe Kazuyuki, Kashiwagi Atsunori, Kawamori Ryuzo, Jia Weiping, Chan Juliana C. N., Teo Yik Ying, Shyong Tai E., Kamatani Naoyuki, Kubo Michiaki, Maeda Shiro, Kadowaki Takashi

HUMAN MOLECULAR GENETICS 23 （ 1 ） 239 - 246 2014年01月

ISSN  0964-6906

　概要を見る

<p>Although over 60loci for type 2 diabetes (T2D) havebeenidentified, there still remains a large geneticcomponent to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele 5 A; risk allele frequency (RAF) 5 0.080; P 5 2.55 × 10^-13; odds ratio (OR) 5 1.17], GPSM1 [rs11787792; risk allele 5 A; RAF 5 0.874; P 5 1.74 × 10^-10; OR 5 1.15] and SLC16A13 (rs312457; risk allele 5 G; RAF 5 0.078; P 5 7.69 × 10^-13; OR 5 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases. © The Author 2013. Published by Oxford University Press. All rights reserved.</p>

• Access to Document (DOI)

Disturbed tumor necrosis factor system is linked with lower eGFR and chronic inflammation in hypertension

Eguchi Takashi, Maruyama Tatsuya, Ohno Yoichi, Morii Toshiyuki, Hirose Hiroshi, Takenaka Tsuneo, Suzuki Hiromichi, Kawabe Hiroshi, Saito Ikuo, Hayashi Matsuhiko, Itoh Hiroshi

INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS 29 （ 1 ） E69 - E77 2014年

ISSN  0393-6155

　概要を見る

<p>Background: The relationship between tumor necrosis factor (TNF)-related parameters and cardiorenal metabolic factors is still controversial in clinical hypertension. Methods: Normotensive men (NT, n=60) and treated stage 2 and 3 essential hypertensive men (HT, n=89) were enrolled in this study. The relationship between TNF-related parameters and cardiorenal metabolic factors was examined in NT and HT, separately. Results: HT showed higher rates of insulin resistance and enhanced chronic inflammation compared with NT. The levels of soluble TNF receptor 1 and 2 were significantly higher in HT than in NT, although TNF-a levels were unexpectedly lower in HT than in NT. Regression analysis indicated that the TNF-related parameters were closely linked with mild renal dysfunction both in NT and HT, and moderately related to chronic inflammation only in HT. HT taking inhibitors of the renin-angiotensin system showed improved insulin resistance, but no difference in the TNF-related parameters. Conclusion: These results suggest that the disturbed TNF system is closely linked with chronic inflammation rather than with insulin resistance in HT. © 2014 Wichtig Editore.</p>

• Access to Document (DOI)

Effects of Oral Propranolol on Circumscribed Choroidal Hemangioma A Pilot Study

Tanabe, H; Sahashi, K; Kitano, T; Tomita, Y; Saito, AM; Hirose, H

JAMA OPHTHALMOLOGY 131 （ 12 ） 1617 - 1622 2013年12月

ISSN  2168-6165

• Access to Document (DOI)

Assessing the Clinical Utility of a Genetic Risk Score Constructed Using 49 Susceptibility Alleles for Type 2 Diabetes in a Japanese Population

広瀬 寛

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 98 （ 10 ） E1667 - E1673 2013年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0021-972X

• Access to Document (DOI)

A Novel, Rapid, Effective, Tolerable, and Safe Preparation Using Mosapride Citrate as an Adjunct to Low-volume Polyethylene Glycol Solution for Colonoscopy

広瀬 寛

AMERICAN JOURNAL OF GASTROENTEROLOGY 108   S577 - S577 2013年10月

研究論文（学術雑誌）,  ISSN  0002-9270

• Access to Document (DOI)

Replication Study for the Association of 9 East Asian GWAS-Derived Loci with Susceptibility to Type 2 Diabetes in a Japanese Population

Sakai Kensuke, Imamura Minako, Tanaka Yasushi, Iwata Minoru, Hirose Hiroshi, Kaku Kohei, Maegawa Hiroshi, Watada Hirotaka, Tobe Kazuyuki, Kashiwagi Atsunori, Kawamori Ryuzo, Maeda Shiro

PLOS ONE 8 （ 9 ）  2013年09月

ISSN  1932-6203

• Access to Document (DOI)

C-Reactive Protein, High-Molecular-Weight Adiponectin and Development of Metabolic Syndrome in the Japanese General Population: A Longitudinal Cohort Study

Saisho Yoshifumi, Hirose Hiroshi, Roberts Rachel, Abe Takayuki, Kawabe Hiroshi, Itoh Hiroshi

PLOS ONE 8 （ 9 ）  2013年09月

ISSN  1932-6203

• Access to Document (DOI)

Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY) (vol 2013, 587140, 2013)

広瀬 寛

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY    587140 - 587140 2013年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1687-8337

• Access to Document (DOI)

Replication study for the association of a single-nucleotide polymorphism, rs3746876, within KCNJ15, with susceptibility to type 2 diabetes in a Japanese population

広瀬 寛

JOURNAL OF HUMAN GENETICS 58 （ 7 ） 490 - 493 2013年07月

研究論文（学術雑誌）,  ISSN  1434-5161

• Access to Document (DOI)

Usefulness of Genetic Risk Score Constructed from 47 Loci for Type 2 Diabetes in Non-Obese, Older Japanese Individuals

Imamura Minako, Iwata Minoru, Maegawa Hiroshi, Watada Hirotaka, Hirose Hiroshi, Tanaka Yasushi, Tobe Kazuyuki, Kaku Kohei, Kashiwagi Atsunori, Kawamori Ryuzo, Maeda Shiro

DIABETES 62   A433 - A433 2013年07月

ISSN  0012-1797

Cost-utility analysis of cataract surgery in Japan: a probabilistic Markov modeling study

Hiratsuka, Y; Yamada, M; Akune, Y; Murakami, A; Okada, AA; Yamashita, H; Ohashi, Y; Yamagishi, N; Tamura, H; Fukuhara, S; Takura, T; Eguchi, S; Akune, Y; Yamada, M; Kurosaka, D; Takahashi, K; Miyake, S; Hirose, H; Otori, Y

JAPANESE JOURNAL OF OPHTHALMOLOGY 57 （ 4 ） 391 - 401 2013年07月

ISSN  0021-5155

• Access to Document (DOI)

Genome-Wide Association Study Identifies a Novel Locus Contributing to Type 2 Diabetes Susceptibility in Sikhs of Punjabi Origin From India

広瀬 寛

DIABETES 62 （ 5 ） 1746 - 1755 2013年05月

研究論文（学術雑誌）,  ISSN  0012-1797

• Access to Document (DOI)