Development of prediction model for cardiovascular diseases and novel therapeutic methods

• Project/Area Number: 16K01838
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Tokyo Medical University
• Principal Investigator: Odawara Masato 東京医科大学, 医学部, 教授 (00224254)
• Research Collaborator: HARA KAZUO
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ゲノム解析 / 感受性遺伝子 / 心血管疾患 / 疾患感受性遺伝子 / 遺伝素因 / ファーマコゲノミクス / ２型糖尿病 / 残余リスク / ゲノム / 遺伝子

Outline of Final Research Achievements

DNA was extracted from patients with lifestyle-related diseases visiting our hospital, and DNA analysis was performed with a next-generation sequencer. It was suggested that, even in general lifestyle-related diseases, these genetic variations are associated with cardiovascular risk and explain at least a part of the residual risk of cardiovascular diseases. Our exome analysis identified a case with a gene mutation that were not previously reported to be associated with cardiovascular disease. Functional analysis confirmed a decrease in enzyme activity of the gene product.

Academic Significance and Societal Importance of the Research Achievements

比較的稀な単一遺伝子病の原因遺伝子に認められる高頻度の遺伝子多型が心血管疾患リスクに一定の影響を与えていることが示唆されたことで、今後症例数を増やした検討によってそれらの遺伝情報を取り入れたより精度の高い生活習慣病患者の心血管リスク評価法の開発が期待できる。また、全く予期しない遺伝子変異を同定しその機能解析から何らかの病態に関与していることが示唆された。今後更に症例数を増やした遺伝疫学的解析と、個体レベルでの機能解析を組み合わせることによって、心血管疾患発症における役割の解明のみならず新規治療法の開発につながることが期待される。

Research Products

• [Journal Article] Structural basis and genotype–phenotype correlations of INSR mutations causing severe insulin resistance (2017)
  • Author(s): Hosoe J, Kadowaki H, Miya F, Aizu K, Kawamura T, Miyata I, Satomura K, Ito T, Hara K, Tanaka M, Ishiura H, Tsuji S, Suzuki K, Takakura M, Boroevich KA, Tsunoda T, Yamauchi T, Shojima N, Kadowaki T
  • Journal Title: Diabetes Volume: 66 Issue: 10 Pages: 2713
  • DOI: 10.2337/db17-0301
  • NAID: 40021637919
  • Peer Reviewed / Open Access / Int'l Joint Research