Search for novel MODY genes with exome sequencing

• Project/Area Number: 23591319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Wakayama Medical University
• Principal Investigator: FURUTA Hiroto 和歌山県立医科大学, 医学部, 准教授 (90238684)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 糖尿病 / 遺伝因子 / ＭＯＤＹ / MODY

Research Abstract

Maturity-onset diabetes of the young (MODY) is a diabetes characterized by an autosomal-dominant mode of inheritance and an onset before the age of 25 years. Although thirteen MODY genes have been reported, a major susceptibility gene in Japanese MODY families has not been identified. In this study, we determined susceptibility genes in 8 Japanese MODY families (p.T228M, p.G246R, p.C371Y and p.G446D in glucokinase, p.E274K in HNF-1A, p.R276H and p.S461I in HNF-1B, p.P1198L in ABCC8) with Sanger sequencing. Furthermore, we carried out whole-exome sequencing which is the targeted sequencing of the human genome region that is protein coding to identify a new susceptibility gene for MODY. We obtained 50 X median coverage of the entire targeted exome and found several rare non-synonymous variants co-segregated with diabetes in a MODY family.

Research Products

• [Journal Article] Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese (2014)
  • Author(s): Ma RC, Lee HM, Lam VK, Tam CH, Ho JS, Zhao HL, Guan J, Kong AP, Lau E, Zhang G, Luk A, Wang Y, Tsui SK, Chan TF, Hu C, Jia WP, Park KS, Lee HK, Furuta H, Nanjo K, Tai ES, Ng DP, Tang NL, Woo J, Leung PC, Xue H, Wong J, Leung PS, Lau TC, Tong PC, Xu G, Ng MC, So WY, Chan JC
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese. (2014)
  • Author(s): Ma RC, Lee HM, Lam VK, Tam CH, Ho JS, Zhao HL, Guan J, Kong AP, Lau E, Zhang G, Luk A, Wang Y, Tsui SK, Chan TF, Hu C, Jia WP, Park KS, Lee HK, Furuta H, Nanjo K, Tai ES, Ng DP, Tang NL, Woo J, Leung PC, Xue H, Wong J, Leung PS, Lau TC, Tong PC, Xu G, Ng MC, So WY, Chan JC
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e84770-e84770
  • DOI: 10.1371/journal.pone.0084770
  • Peer Reviewed
• [Journal Article] Genetic associations of type 2 diabetes with islet amyloid polypeptide processing and degrading pathways in asian populations (2013)
  • Author(s): Lam VK, Ma RC, Lee HM, Hu C, Park KS, Furuta H, Wang Y, Tam CH, Sim X, Ng DP, Liu J, Wong TY, Tai ES, Morris AP; DIAGRAM Consortium, Tang NL, Woo J, Leung PC, Kong AP, Ozaki R, Jia WP, Lee HK, Nanjo K, Xu G, Ng MC, So WY, Chan JC
  • Journal Title: PLoS One Volume: 8(6)
  • Peer Reviewed
• [Journal Article] Clinical and functional characterization of the Pro1198Leu ABCC8 gene mutation associated with permanent neonatal diabetes mellitus (2013)
  • Author(s): Takagi T, Furuta H, Miyawaki M, Nagashima K, Shimada T, Doi A, Matsuno S, Tanaka D, Nishi M, Sasaki H, Inagaki N, Yoshikawa N, Nanjo K, Akamizu T
  • Journal Title: J Diabetes Invest Volume: 4 Pages: 269-273
  • Peer Reviewed
• [Journal Article] The Kir6.2 E23K polymorphism is related to secondary failure of sulfonylureas in non-obese patients with type 2 diabetes (2013)
  • Author(s): Shimajiri Y, Yamana A, Morita S, Furuta H, Furuta M, Sanke T
  • Journal Title: J Diabetes Invest Volume: 4(5) Pages: 445-449
  • Peer Reviewed
• [Journal Article] Clinical and functional characterization of the Pro1198Leu ABCC8 gene mutation associated with permanent neonatal diabetes mellitus. (2013)
  • Author(s): Takagi T, Furuta H, Miyawaki M, Nagashima K, Shimada T, Doi A, Matsuno S, Tanaka D, Nishi M, Sasaki H, Inagaki N, Yoshikawa N, Nanjo K, Akamizu T.
  • Journal Title: J Diabetes Invest Volume: 4 Issue: 3 Pages: 269-273
  • DOI: 10.1111/jdi.12049
  • Peer Reviewed
• [Journal Article] The Kir6.2 E23K polymorphism is related to secondary failure of sulfonylureas in non-obese patients with type 2 diabetes. (2013)
  • Author(s): Shimajiri Y, Yamana A, Morita S, Furuta H, Furuta M, Sanke T
  • Journal Title: J Diabetes Invest Volume: 4 Issue: 5 Pages: 445-449
  • DOI: 10.1111/jdi.12070
  • Peer Reviewed
• [Journal Article] Genetic associations of type 2 diabetes with islet amyloid polypeptide processing and degrading pathways in asian populations. (2013)
  • Author(s): Lam VK, Ma RC, Lee HM, Hu C, Park KS, Furuta H, Wang Y, Tam CH, Sim X, Ng DP, Liu J, Wong TY, Tai ES, Morris AP; DIAGRAM Consortium, Tang NL, Woo J, Leung PC, Kong AP, Ozaki R, Jia WP, Lee HK, Nanjo K, Xu G, Ng MC, So WY, Chan JC
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: e62378-e62378
  • DOI: 10.1371/journal.pone.0062378
  • Peer Reviewed
• [Journal Article] Defective PAX4 R192H transcriptional repressor activities associated with maturity onset diabetes of the young and early onset-age of type 2 diabete (2012)
  • Author(s): Kooptiwut S, Plengvidhya N, Chukijrungroat T, Sujjitjoon J, Semprasert N, Furuta H, Yenchitsomanus PT
  • Journal Title: J Diabetes Complications Volume: 26 Pages: 343-347
  • Peer Reviewed
• [Journal Article] Defective PAX4 R192H transcriptional repressor activities associated with maturity onset diabetes of the young and early onset-age of type 2 diabete. (2012)
  • Author(s): Kooptiwut S, Plengvidhya N, Chukijrungroat T, Sujjitjoon J, Semprasert N, Furuta H, Yenchitsomanus PT
  • Journal Title: J Diabetes Complications Volume: 26 Pages: 343-347
  • Peer Reviewed
• [Journal Article] Komori T, Doi A, Nosaka T, Furuta H, Akamizu T, Kitamura T, Senba E, Morikawa Y: Regulation of AMP-activated protein kinase signaling by AFF4, a member of the AF4 (ALL1-fused gene from chromosome 4) family of transcription factors, in hypothalamic neurons. (2012)
  • Author(s): Komori T, Doi A, Nosaka T, Furuta H, Akamizu T, Kitamura T, Senba E, Morikawa Y
  • Journal Title: J Biol Chem Volume: in press
  • Peer Reviewed
• [Journal Article] Pro 198 Leu missense polymorphism of the glutathione peroxidase 1 gene might be a common genetic predisposition of distal symmetric polyneuropathy and macrovascular disease in Japanese type 2 diabetic patient. (2011)
  • Author(s): Matsuno S, Sasaki H, Yamazaki H, Yamaoka H, Ogawa K,,Nakatani M, Hamanishi T, Doi A, Nakano Y, Wakasaki H, Furuta H, Nishi M, Akamizu T, Nanjo K
  • Journal Title: J Diabetes Invest Volume: in press
  • Peer Reviewed
• [Presentation] ABCC8遺伝子変異による糖尿病の臨床的特長 (2014)
  • Author(s): 古田浩人、浦木進丞、高木伴幸、土井麻子、宮脇正和、島友子、西理宏、吉川徳茂、赤水尚史
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-05-24
• [Presentation] 遺伝子診断が治療法の決定に有用であった若年発症糖尿病の1例 (2013)
  • Author(s): 浦木進丞、古田浩人、飯島文憲、宮脇正和、土井麻子、有安宏之、川嶋弘道、若﨑久生、西理宏、吉川徳茂、赤水尚史
  • Organizer: 第50回日本糖尿病学会近畿地方会
  • Place of Presentation: 京都市
  • Year and Date: 2013-11-23
• [Presentation] 遺伝子診断後にインスリンからSU薬に治療を変更しえたABCC8遺伝子変異による新生児糖尿病の2例 (2013)
  • Author(s): 浦木進丞、高木伴幸、古田浩人、島友子、川嶋弘道、宮脇正和、長嶋一昭、土井麻子、島田健、若﨑久生、西理宏、中尾大成、佐々木秀行、稲垣暢也、南條輝志男、赤水尚史
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市
  • Year and Date: 2013-05-18
• [Presentation] Clinical and functional characterization of the Pro1198Leu ABCC8 gene mutation associated with permanent neonatal diabetes mellitus (2013)
  • Author(s): Furuta H, Takagi T, Miyawaki M, Nagashima K, Shimada T, Doi A, Matsuno S, Tanaka D, Nishi M, Sasaki H, Inagaki N, Yoshikawa N, Nanjo K, Akamizu T
  • Organizer: βCell Workshop 2013
  • Place of Presentation: Kyoto, Japan
• [Presentation] 遺伝子診断後にインスリンからSU薬に治療を変更しえたABCC8遺伝子変異による新生児糖尿病の２例． (2013)
  • Author(s): 浦木進丞、高木伴幸、古田浩人、島 友子、川嶋弘道、宮脇正和、長嶋一昭、土井麻子、島田 健、若﨑久生、西 理宏、中尾大成、佐々木秀行、稲垣暢也、南條輝志男、赤水尚史
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市
• [Presentation] Genetic Prediction of Type 2 Diabetes (2012)
  • Author(s): Furuta, H
  • Organizer: 9th IDF-WPR Congress & 4th AASD Scientific Meeting
  • Place of Presentation: Kyoto, Japan
• [Presentation] 2型糖尿病疾患感受性遺伝子多型とグルカゴンによるインスリン分泌との関係 (2011)
  • Author(s): 古田浩人、松野正平, 古川安志, 土井麻子, 西理宏, 佐々木秀行, 三家登喜夫, 南條輝志男, 赤水尚史
  • Organizer: 第54回日本糖尿病学会年次学術総会
  • Place of Presentation: 札幌
• [Presentation] 学童検診での尿糖陽性が診断の契機となったMODY2の1家系 (2011)
  • Author(s): 1.遠藤久子、古田浩人、松野正平、土井麻子、高木伴幸、西理宏, 佐々木秀行, 南條輝志男, 赤水尚史
  • Organizer: 第48回日本糖尿病学会近畿地方会
  • Place of Presentation: 大阪
• [Presentation] 遺伝子診断が治療法の決定に有用であった若年発症糖尿病の１例
  • Author(s): 浦木進丞、古田浩人、飯島文憲、宮脇正和、土井麻子、有安宏之、川嶋弘道、若﨑久生、西 理宏、吉川徳茂、赤水尚史
  • Organizer: 第50回日本糖尿病学会近畿地方会
  • Place of Presentation: 京都市
• [Book] 「すべてがわかる最新・糖尿病」、編集 門脇孝、 (2011)
  • Author(s): 古田浩人（分担執筆）
  • Total Pages: 450
  • Publisher: 照林社