Identification of novel susceptibility variants to type 1 diabetes by a next-generation sequencing

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591321
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Saitama Medical University
• Principal Investigator: AWATA TAKUYA 埼玉医科大学, 医学部, 教授 (40184303)
• Co-Investigator(Renkei-kenkyūsha): KURIHARA Susumu 埼玉医科大学, 医学部, 准教授 (90286104) ; MORITA Tomoko 埼玉医科大学, 医学部, 講師 (40348214) ; IIZUKA Hiroyuki 埼玉医科大学, 医学部, 助教 (20348246)
• Project Period (FY): 2011 – 2013
• Keywords: １型糖尿病 / 疾患感受性遺伝子 / SNP / バリアント / GLIS3 / 日本人

Research Abstract

In Japanese, HLA class II is a very strong susceptibility factor, and the insulin gene is another confirmed susceptible locus to type 1 diabetes (T1D). We have also obtained evidence for an association with several non-HLA loci. However, it was revealed that the cumulative effect of these non-HLA susceptibility loci was much weaker than that of the HLA class II loci.
Thus, in the present study, we analyzed low-frequency variants of the non-HLA T1D candidate genes in Japanese. We first screened for protein-changing variants of 24 T1D candidate genes and then the association with T1D was tested in 706 T1D patients and 863 control subjects. In total, 56 protein-changing variants were discovered; among them, 34 were low-frequency variants. The association analysis of the low-frequency variants revealed that only the A908V variant of GLIS3 was strongly associated with resistance to T1D. This is the first report on association of low-frequency variants with T1D in non-white populations.

Research Products

• [Journal Article] A low-frequency GLIS3 variant associated with resistance to Japanese type 1 diabetes (2013)
  • Author(s): Awata T, Yamashita H, Kurihara S, Morita-Ohkubo T, Miyashita Y, Katayama S, Kawasaki E, Tanaka S, Ikegami H, Maruyama T, Shimada A, Takahashi K, Kawabata Y, Kobayashi T, Nishida N, Mawatari Y
  • Journal Title: Biochem Biophys Res Commun Volume: 437 Pages: 521-525
  • Peer Reviewed
• [Journal Article] 1型糖尿病遺伝子解析の最新情報 (2012)
  • Author(s): 粟田卓也、山下富都
  • Journal Title: 月刊糖尿病 Volume: 4(9) Pages: 120-130
• [Journal Article] 1型糖尿病の遺伝因子～特に日本と欧米の共通点・相違点について～ (2012)
  • Author(s): 粟田卓也
  • Journal Title: Diabetes Frontier Volume: 23(3) Pages: 267-278
• [Presentation] 1型糖尿病関連遺伝子 (2013)
  • Author(s): 粟田卓也
  • Organizer: 第47回糖尿病学の進歩
  • Place of Presentation: 三重県四日市
  • Year and Date: 2013-02-15
  • Invited
• [Presentation] A rare GLIS3 variant associated with resistance to type 1 diabetes (2012)
  • Author(s): Takuya Awata, Susumu Kurihara, Tomoko Morita-Ohkubo, Yumi Miyashita, Eiji Kawasaki, Hiroshi Ikegami, Shoichiro Tanaka, Taro Maruyama, Akira Shimada, Kazuma Takahashi, Yumiko Kawabata, Tetsuro Kobayashi.
  • Organizer: The 48th Annual Meeting of the European Association for the Study of Diabetes (EASD)
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-10-04
• [Book] 急性発症典型1型糖尿病.日本臨床70巻増刊号3(最新臨床糖尿病学・上) (2012)
  • Author(s): 粟田卓也
  • Total Pages: 358-364
  • Publisher: 日本臨牀社、大阪