Basic research for personalized medicine for cerebral infarction

• Project/Area Number: 17K16627
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: The University of Tokyo
• Principal Investigator: Miyawaki Satoru 東京大学, 医学部附属病院, 講師 (70407914)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 脳梗塞 / ＲＮＦ213 / 頭蓋内動脈硬化 / 修飾因子 / RNF213 / 頭蓋内狭窄 / リスクアレル

Outline of Final Research Achievements

We conducted integrated research on stroke-related genetic variant RNF213 c.14576G> A, especially important for Japanese population. The characteristics of intracranial artery stenosis with RNF 213 c.14576 G> A has been revealed. In addition, we clarified the genetic factors involved in the onset of cerebral infarction in intracranial artery stenosisi, and it became clear that they differ depending on the presence or absence of RNF213 c.14576G> A. In addition to RNF213 c.14576G> A, genetic factors related to the onset of intracranial major arterial stenosis has been identified through genome wide association study.

Academic Significance and Societal Importance of the Research Achievements

頭蓋内主幹動脈狭窄に限った臨床的・遺伝的背景の解析は世界的には少なく、学術的意義は高いと考えられる。RNF213 c.14576G>Aは日本人の2%が有する遺伝子変異である、その臨床的意義を明らかにした本研究は社会的意義が大きいと考える。

Research Products

• [Journal Article] Response to Letter to the Editor Regarding “Genetic Analysis of Ring Finger Protein 213 (RNF213) c.14576G>A in Intracranial Atherosclerosis of the Anterior and Posterior Circulations” (2018)
  • Author(s): Miyawaki Satoru、Shinya Yuki、Imai Hideaki、Hongo Hiroki、Ono Hideaki、Takenobu Atsumi、Nakatomi Hirofumi、Teraoka Akira、Saito Nobuhito
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 27 Issue: 10 Pages: 2894-2895
  • DOI: 10.1016/j.jstrokecerebrovasdis.2018.07.009
  • Peer Reviewed / Open Access
• [Journal Article] Short review of randomized controlled trials (RCTs) for Surgical Neurology International: Two important RCT articles for 2018 - Part I. (2018)
  • Author(s): Lo BWY, Fukuda H, Miyawaki S, Koyanagi M
  • Journal Title: Surg Neurol Int. Volume: 9 Issue: 1 Pages: 138-138
  • DOI: 10.4103/sni.sni_179_18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Referee Report For: The future of non-invasive cerebral oximetry in neurosurgical procedures: A systematic review [version 1; referees: 1 approved with reservations]. (2018)
  • Author(s): Miyawaki S.
  • Journal Title: MNI Open Res Volume: 2 Pages: 3-3
  • Peer Reviewed
• [Journal Article] Microsurgery Simulator of Cerebral Aneurysm Clipping with Interactive Cerebral Deformation Featuring a Virtual Arachnoid (2017)
  • Author(s): Shono Naoyuki、Kin Taichi、Nomura Seiji、Miyawaki Satoru、Saito Toki、Imai Hideaki、Nakatomi Hirofumi、Oyama Hiroshi、Saito Nobuhito
  • Journal Title: Operative Neurosurgery Volume: 0 Issue: 5 Pages: 1-11
  • DOI: 10.1093/ons/opx155
  • Peer Reviewed / Open Access
• [Journal Article] Genetic Analysis of RNF213 c.14576G>A in Intracranial Atherosclerosis of the Anterior and Posterior Circulation. (2017)
  • Author(s): Shinya Y, Miyawaki S, Imai H, Hongo H, Ono H, Takenobu A, Nakatomi H, Teraoka A and Saito N.
  • Journal Title: Stroke Cerebrovasc Dis Volume: 26(11) Issue: 11 Pages: 2638-2644
  • DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.043
  • Peer Reviewed / Open Access
• [Journal Article] Smaller Outer Diameter of Atherosclerotic Middle Cerebral Artery Associated with RNF213 c.14576G>A Variant (rs112735431). (2017)
  • Author(s): Hongo H, Miyawaki S, Imai H, Shinya Y, Hideaki O, Mori H, Nakatomi H, Kunimatsu A, Saito N.
  • Journal Title: Surg Neurol Int Volume: 5;8 Issue: 1 Pages: 104-104
  • DOI: 10.4103/sni.sni_59_17
  • Peer Reviewed / Open Access
• [Journal Article] Genetic analysis of intracranial major artery stenosis: Analysis of moyamoya disease associated gene <i>RNF213</i> (2017)
  • Author(s): 宮脇哲、今井英明、斉藤延人
  • Journal Title: Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism) Volume: 28 Issue: 2 Pages: 341-345
  • DOI: 10.16977/cbfm.28.2_341
  • NAID: 130006008205
  • ISSN: 0915-9401, 2188-7519
  • Peer Reviewed / Open Access
• [Journal Article] 動脈・静脈の疾患(臓器別) 脳血管疾患 くも膜下出血 病因と病態 (2017)
  • Author(s): 宮脇哲、斉藤延人
  • Journal Title: 日本臨牀 Volume: 75巻増刊5 Pages: 647-651
• [Presentation] 頭蓋内狭窄病変の遺伝的要因と病態－RNF213変異を中心とした頭蓋内狭窄の解析－ (2018)
  • Author(s): 宮脇哲1, 今井英明1, 清水暢裕2, 八木伸一2, 本郷 博貴1, 新谷祐貴3, 岡野淳1, 寺西裕1, 小野秀明3, 寺岡暉4, 中冨浩文1, 清水庸夫2, 斉藤延人1 1 東京大学 医学部 脳神経外科 2 関東脳神経外科病院 3 富士脳障害研究所附属病院 4 寺岡記念病院
  • Organizer: 第43回日本脳卒中学会
• [Presentation] Genetic analysis of RNF213 c.14575G>A variant in Moyamoya disease and related diseases. (2018)
  • Author(s): Satoru Miyawaki, Hideaki Imai, Nobuhito Saito.
  • Organizer: 9th European - Japanese Cerebrovascular Congress.
  • Int'l Joint Research
• [Presentation] 質量顕微鏡法を用いた虚血性神経細胞死の解析 (2017)
  • Author(s): 宮脇哲1, 今井英明1, 早坂孝宏2, 正木紀隆3, 小野秀明1, 越智崇1, 中冨浩文1, 瀬藤光利3, 斉藤延人1 1 東京大学 医学部 脳神経外科 2 北海道大学 大学院保健科学研究院 健康イノベーションセンター 3 浜松医科大学 医学部 解剖学講座細胞生物学分野
  • Organizer: 第42回日本卒中学会
• [Presentation] Dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia detected by imaging mass spectrometry. (2017)
  • Author(s): Satoru Miyawaki， Hideaki Imai， Takahiro Hayasaka， Noritaka Masaki, Hideaki Ono， Takashi Ochi, Hirofumi Nakatomi, Mitsutoshi Setou，Nobuhito Saito
  • Organizer: XXVIIIth International Symposium on Cerebral Blood Flow, Metabolism and Function & XIIIth International Conference on Quantification of Brain Function with PET
• [Presentation] 頭蓋内主幹動脈狭窄の遺伝子解析 (2017)
  • Author(s): 宮脇哲
  • Organizer: 第13回 福岡脳神経血管内治療シナプス
• [Presentation] 虚血性脳血管障害におけるPrecision medicine (2017)
  • Author(s): 宮脇哲、今井英明、斉藤延人
  • Organizer: 第37回日本脳神経外科コングレス総会
• [Presentation] Current trends and issues of moyamoya disease (2017)
  • Author(s): 宮脇哲
  • Organizer: 第11回Niche Neuro-Angiology Conference
• [Presentation] もやもや病感受性遺伝子RNF213の解析（シンポジウム） (2017)
  • Author(s): 宮脇哲、今井英明、斉藤延人
  • Organizer: 第49回日本動脈硬化学会総会・学術集会
• [Presentation] Spatio-temporal changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia detected by imaging mass spectrometry (2017)
  • Author(s): Satoru Miyawaki， Hideaki Imai， Takahiro Hayasaka， Noritaka Masaki, Hideaki Ono， Takashi Ochi, Hirofumi Nakatomi, Mitsutoshi Setou，Nobuhito Saito
  • Organizer: 第40回日本神経科学大会
• [Presentation] Genetic analysis of Moyamoya disease and Intracranial stenosis (2017)
  • Author(s): Satoru Miyawaki, Hideaki Imai, Nobuhito Saito
  • Organizer: 2017 Pudong Cerebral Vascular Disease Conference
• [Presentation] Current trends and issues of genetic analysis of moyamoya disease (2017)
  • Author(s): 宮脇哲, 今井英明, 斉藤延人
  • Organizer: 第76回日本脳神経外科学会学術総会
• [Presentation] もやもや病の遺伝子解析研究の現況と今後の展望（シンポジウム） (2017)
  • Author(s): 宮脇哲, 今井英明, 斉藤延人
  • Organizer: 第60回日本脳循環代謝学会学術集会 2017.11.4
• [Presentation] 頭蓋内主幹動脈狭窄疾患におけるRNF213の解析 (2017)
  • Author(s): 宮脇哲, 今井英明, 斉藤延人
  • Organizer: 日本人類遺伝学会 第62回大会
• [Book] 完全版 脳血管内治療学 (2018)
  • Author(s): 宮脇哲、斉藤延人。
  • Total Pages: 512
  • Publisher: メディカ出版
  • ISBN: 9784840464895
• [Book] Moyamoya Disease Explored Through RNF213 (2017)
  • Author(s): Miyawaki S, Imai H, Saito N.
  • Total Pages: 185
  • Publisher: Springer
  • ISBN: 9789811027116
• [Book] クリニカルニューロサイエンス (2017)
  • Author(s): 宮脇哲
  • Publisher: 中外医学社
• [Book] 脳血管障害のエッセンス (2017)
  • Author(s): 宮脇哲、斉藤延人
  • Publisher: 日本医師会