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Challenge for prevention of sudden unexplained death : Elucidation of molecular mechanisms of death by transomics analysis

Research Project

Project/Area Number 18H04078
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 58:Society medicine, nursing, and related fields
Research InstitutionOsaka University

Principal Investigator

MATSUMOTO HIROSHI  大阪大学, 大学院医学系研究科, 教授 (60263092)

Co-Investigator(Kenkyū-buntansha) 杉本 香奈  大阪大学, 医学系研究科, 講師 (00581034)
東阪 和馬  大阪大学, 医学系研究科, 特任講師(常勤) (20646757)
原田 和生  大阪大学, 医学系研究科, 特任准教授(常勤) (50397741)
宮下 洋平  大阪大学, 医学系研究科, 助教 (60816312)
吉澤 秀憲  大阪大学, 医学部附属病院, 医員 (90739905)
山田 知美  大阪大学, 医学部附属病院, 特任教授(常勤) (60363371)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥41,860,000 (Direct Cost: ¥32,200,000、Indirect Cost: ¥9,660,000)
Fiscal Year 2020: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2018: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Keywords突然死 / 全エクソーム解析 / メタボロミクス解析 / 自律神経関連遺伝子 / 心疾患関連遺伝子 / 副交感神経 / 心肥大 / ゲノム変異解析 / オミックス解析 / エクソーム解析 / 死因究明学 / ゲノム変異 / 死因究明 / 致死的遺伝子 / 死因診断マーカ / 動物モデル解析 / メタゲノム解析 / 心疾患関連遺伝子変異 / 自律神経関連遺伝子変異 / 乳幼児突然死 / ゲノム / 腸内細菌メタゲノム / メタボロミクス
Outline of Final Research Achievements

This was a study to elucidate some of the mechanisms of sudden death of unknown cause by omics analysis such as genomic analysis. Comparing sudden death, cardiac hypertrophy, and other causes of death, there was no significant difference in the number of genomic variants related to so-called cardiac disease between the sudden death group and the cardiac hypertrophy group, but there was a clear difference in the X gene mutation. The number of mutations in the autonomic nervous system-related genes was also examined, and the number of mutations in the sudden death group was clearly higher, indicating that the autonomic nervous system is greatly involved in the pathogenesis of sudden death, and revealing a part of the molecular mechanism of sudden death and suggesting its therapeutic application. The results of this study suggest that the molecular mechanism of sudden death and its therapeutic application may be important in the treatment of sudden death.

Academic Significance and Societal Importance of the Research Achievements

突然死は毎年7万~12万人に見積もられているものの、現在の健康診断や医療では発症予測や予防が難しい。今回この研究において、40歳以上の突然死群においては通常よりも剖検心重量が有意に軽いこと、一方で、心肥大群と比較したところ心疾患遺伝子群の変異数に有意差が無い一方で、自律神経関連遺伝子群の変異数が有意に多く特に副交感神経関連遺伝子群の変異が多いことが明らかになった。このことは心肥大を伴わない突然の心停止者に対して副交感神経活性化の治療が蘇生につながる臨床的応用の可能性があり、少なくとも2~3万人の命を救うことができ、学術的意義のみならず労働人口の減少を食い止める意味でも社会的意義は大きい。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (9 results)

All 2023 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 4 results)

  • [Journal Article] Molecular mechanism of cerebral edema improvement via IL-1RA released from stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats2023

    • Author(s)
      Gono R, Sugimoto K, Yang C, Murata Y, Nomura R, Shirazaki M, Harada K, Harada T, Miyashita Y, Higashisaka K, Katada R, Matsumoto H
    • Journal Title

      J Cereb. Blood Flow Metab

      Volume: 43 Issue: 5 Pages: 812-827

    • DOI

      10.1177/0271678x231151569

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of Quantitative Values of Headspace Gas Chromatography--Mass Spectrometry and a Formate Quantification Kit in Blood Formate Quantification.2023

    • Author(s)
      Yoshida H, Harada K, Sakamoto Y, Yoshimura J, Shimazu T, Matsumoto H
    • Journal Title

      J Anal Toxicol.

      Volume: 47 Issue: 4 Pages: 338-345

    • DOI

      10.1093/jat/bkac107

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An Autopsy Case Report of Homicide by Methanol Intoxication With Pinkish Bilateral Putamina2022

    • Author(s)
      Takahashi Motonori、Kondo Takeshi、Yamasaki Gentaro、Sugimoto Marie、Yoshida Haruhi、Harada Kazuo、Matsumoto Hiroshi、Asano Migiwa、Ueno Yasuhiro
    • Journal Title

      American Journal of Forensic Medicine & Pathology

      Volume: 44 Issue: 1 Pages: 55-58

    • DOI

      10.1097/paf.0000000000000790

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated cardiomyopathy requiring heart transplantation.2022

    • Author(s)
      Hakui H, Kioka H, Miyashita Y, Nishimura S, Matsuoka K, Kato H, Tsukamoto O, Kuramoto Y, Takuwa A, Takahashi Y, Saito S, Ohta K, Asanuma H, Fu HY, Shinomiya H, Yamada N, Ohtani T, Sawa Y, Kitakaze M, Takashima S, Sakata Y, Asano Y.
    • Journal Title

      Sci Transl Med

      Volume: 14

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Barium-induced toxic anterior segment syndrome2021

    • Author(s)
      Matsushita Kenji、Kawashima Rumi、Hashida Noriyasu、Hamano Yuki、Harada Kazuo、Higashisaka Kazuma、Baba Koichi、Sato Shigeru、Huang Weiran、Matsumoto Hiroshi、Hamanaka Teruhiko、Quantock Andrew J.、Nishida Kohji
    • Journal Title

      European Journal of Ophthalmology

      Volume: 1 Issue: 3 Pages: 1-5

    • DOI

      10.1177/11206721211069223

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures2021

    • Author(s)
      Shimojima Yamamoto Keiko、Yanagishita Tomoe、Yamamoto Hisako、Miyamoto Yusaku、Nagata Miho、Ishihara Yasuki、Miyashita Yohei、Asano Yoshihiro、Sakata Yasushi、Yamamoto Toshiyuki
    • Journal Title

      Human Genome Variation

      Volume: 8 Issue: 1 Pages: 43-43

    • DOI

      10.1038/s41439-021-00176-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activated microglia-derived macrophage-like cells exacerbate brain edema after ischemic stroke correlate with astrocytic expression of aquaporin-4 and interleukin-1 alpha release2020

    • Author(s)
      Murata Yukie、Sugimoto Kana、Yang Chihpin、Harada Kazuo、Gono Rina、Harada Teiji、Miyashita Yohei、Higashisaka Kazuma、Katada Ryuichi、Tanaka Junya、Matsumoto Hiroshi
    • Journal Title

      Neurochemistry International

      Volume: 140 Pages: 104848-104848

    • DOI

      10.1016/j.neuint.2020.104848

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanisms of Wischnewski spot development on gastric mucosa in fatal hypothermia: an experimental study in rats2020

    • Author(s)
      Chihpin Yang, Kana Sugimoto, Yukie Murata, Yuichiro Hirata, Yu Kamakura, Yoshihisa Koyama, Yohei Miyashita, Kentaro Nakama, Kazuma Higashisaka, Kazuo Harada, Ryuichi Katada, Hiroshi Matsumoto
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1877-1877

    • DOI

      10.1038/s41598-020-58894-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development and evaluation of a simultaneous and efficient quantification strategy for final prostanoid metabolites in urine2019

    • Author(s)
      Tian-qi Zhang, Hirotaka Kuroda, Kazuya Nagano, Soshi Terada, Jian-Qing Gao, Kazuo Harada, Kazumasa Hirata, Hirofumi Tsujino, Kazuma Higashisaka, Hiroshi Matsumoto, Yasuo Tsutsumi
    • Journal Title

      Prostaglandins, Leukotrienes and Essential Fatty Acids

      Volume: 6 Pages: 102032-102032

    • DOI

      10.1016/j.plefa.2019.102032

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research

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Published: 2018-04-23   Modified: 2025-01-30  

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