2022 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number	18H04078
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 58:Society medicine, nursing, and related fields
Research Institution	Osaka 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
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
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.
Free Research Field	法医学、死因究明学、突然死ゲノム学、アルコール医学
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。