Functional analysis of GWAS-derived type 2 diabetes susceptibility genes

• Project/Area Number: 26461390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: University of the Ryukyus (2015-2016); The Institute of Physical and Chemical Research (2014)
• Principal Investigator: IMAMURA Minako 琉球大学, 医学(系)研究科(研究院), 准教授 (00596124)
• Co-Investigator(Kenkyū-buntansha): 前田 士郎 琉球大学, 医学(系)研究科(研究院), 教授 (50314159)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 2型糖尿病 / 遺伝要因 / 遺伝子

Outline of Final Research Achievements

We have performed a fine-mapping within the C2CD4A-C2CD4B locus to identify causal variants for type 2 diabetes susceptibility. The most significant association was observed in intergenic region which indicates the causal variant may affect the expression of either C2CD4A or C2CD4B. We also found that these genes dominantly expressed in human pancreas and mouse pancreatic beta cell line. Motivated by the results of fine mapping and expression analysis, we have generated beta-cell specific transgenic mice for C2cd4a and C2cd4b respectively to evaluate the role of these genes in vivo.

Research Products

• [Journal Article] Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies. (2016)
  • Author(s): 2．Matsuba R, Imamura M, Tanaka Y, Iwata M, Hirose H, Kaku K, Maegawa H, Watada H, Tobe K, Kashiwagi A, Kawamori R, Maeda S
  • Journal Title: PLoS One. Volume: 11 Issue: 4 Pages: e0154093-e0154093
  • DOI: 10.1371/journal.pone.0154093
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 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. (2015)
  • Author(s): Matsuba R,, Sakai K, Imamura M, Tanaka Y, Iwata M, Hiroshe H, Kaku K, Maegawa H, WatadaH, Tobe K, Kashiwagi A, Kawamori R, Maeda S.
  • Journal Title: Plos One Volume: 10 Issue: 5 Pages: e0126363-e0126363
  • DOI: 10.1371/journal.pone.0126363
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 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 (2015)
  • Author(s): Sakai K, Imamura M, Tanaka Y, Iwata M, Hirose H, Kaku K, Maegawa H, Watada H, Tobe K, Kashiwagi A, Kawamori R, Maeda S
  • Journal Title: Diabetology International Volume: なし Issue: 4 Pages: 306-312
  • DOI: 10.1007/s13340-015-0202-6
  • NAID: 40020684020
  • Peer Reviewed
• [Presentation] New insights in pathogenesis of type 2 diabetes -From genetics to biology- (2016)
  • Author(s): 今村美菜子, 前田士郎
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都国際会議場 京都市
  • Year and Date: 2016-05-21
  • Invited
• [Presentation] 2型糖尿病GWASの現状 (2015)
  • Author(s): 今村美菜子、前田士郎
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ (山口県下関市)
  • Year and Date: 2015-05-21
  • Invited
• [Presentation] 日本人2型糖尿病集団における糖尿病網膜症のゲノムワイド関連解析 (2014)
  • Author(s): 今村美菜子, 高橋篤、久保充明、前田士郎
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船堀 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] 日本人2型糖尿病集団における糖尿病網膜症のゲノムワイド関連解析 (2014)
  • Author(s): 今村美菜子, 高橋篤、久保充明、前田士郎
  • Organizer: 第29回日本糖尿病合併症学会
  • Place of Presentation: 都市センターホテル 東京
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] Genome-wide association study for diabetic retinopathy in Japanese patients with type 2 diabetes (2014)
  • Author(s): Minako Imamura, Atsushi Takahashi, Michiaki Kubo, Shiro Maeda
  • Organizer: 49th EASD Annual Meeting
  • Place of Presentation: Messe Wien Exhibition & Congress Center, Vienna, Austria
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] Genome-wide Search for Susceptibility Loci to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes (2014)
  • Author(s): Minako Imamura, Atsushi Takahashi, Michiaki Kubo, Shiro Maeda
  • Organizer: American Diabetes Association’s 74th Scientific Sessions
  • Place of Presentation: Moscone Center, San Francisco, California, USA
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] 日本人2型糖尿病集団における糖尿病網膜症のゲノムワイド関連解析 (2014)
  • Author(s): 今村美菜子, 高橋篤、久保充明、前田士郎
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場 大阪
  • Year and Date: 2014-05-22 – 2014-05-24