Identification of susceptibility variants to type 1 diabetes using whole-exome sequencing

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: International University of Health and Welfare (2015-2016); Saitama Medical University (2014)
• Principal Investigator: Awata Takuya 国際医療福祉大学, 大学病院, 教授 (40184303)
• Co-Investigator(Renkei-kenkyūsha): KURIHARA SUSUMU 埼玉医科大学, 医学部, 准教授 (90286104) ; OKAZAKI YASUSHI 埼玉医科大学, 医学部, 教授 (80280733) ; NISHIDA NAO 国立研究開発法人国立国際医療研究センター, 肝炎・免疫研究センター, 上級研究員 (50456109)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: １型糖尿病 / 疾患感受性遺伝子 / 全エクソーム解析 / ２型糖尿病 / トール様受容体 / バリアント / SNP

Outline of Final Research Achievements

We performed whole-exosome sequencing of 21 patients with type 1 diabetes mellitus. Among the detected susceptibility variant candidates, we focused on low-frequency nonsynonymous mutations found in one gene of the Toll-like receptor (TLR) family, which is important for innate immunity. In case-control association tests including over 5000 subjects, the frequency of homozygotes of the mutation was significantly increased in patients with type 1 diabetes, and in a family of type 1 diabetes brothers, it was found that both brothers were homozygotes of this mutation. Interestingly, wild-type alleles were significantly increased in type 2 diabetes. We are currently conducting functional analysis.

Free Research Field

糖尿病