The investigation of genetics and pathophysiological mechanism in hypertrophic cardiomyopathy
| Project/Area Number |
16K09440
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kochi University |
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Principal Investigator |
Kubo Toru 高知大学, 教育研究部医療学系臨床医学部門, 講師 (80325422)
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| Co-Investigator(Kenkyū-buntansha) |
北岡 裕章 高知大学, 教育研究部医療学系臨床医学部門, 教授 (10274375)
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| Project Period (FY) |
2016-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 肥大型心筋症 / 遺伝子解析 / サルコメア遺伝子変異 / 突然死 / 塞栓症 / 心不全 / サルコメア遺伝子 / 予後 / 表現型 / 拡張相肥大型心筋症 / ファブリー病 / 遺伝子型 |
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| Outline of Final Research Achievements |
We performed genetic analysis, pathophysiological evaluation including identification of risk markers, and elucidation of genotype-phenotype correlation in hypertrophic cardiomyopathy (HCM). In genetic analysis, we screened several sarcomere genes in over 200 HCM families. he pathogenic variation analysis, clinical type evaluation, and the relationship between genotype and phenotype in hypertrophic cardiomyopathy. In the pathogenic mutation analysis, mutation screening was performed mainly on the sarcomere protein gene in more than 200 HCM patients. Regarding the clinical impact of presence of those sarcomere mutations, we found that patients with sarcomere gene mutations experienced more frequent HCM-related morbid events. We also identified the risk of sudden death, the risk of embolism, and the risk factors for the progression of left ventricular remodeling of this disease. Identification of these clinical markers is an extremely important finding in clinical management of HCM.
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| Academic Significance and Societal Importance of the Research Achievements |
肥大型心筋症は一般人口の少なくとも500人に1人の頻度で存在する疾患であり、若年者の突然死の原因疾患として最も頻度が高い。本症は遺伝性疾患とされているが、日本人患者を対象にした遺伝子情報と臨床病型との関連性の検討は十分には行われていない。今回の研究で、遺伝子変異の同定される患者は変異非同定患者に比して、予後が不良であることが判明した。このことは本症の病因遺伝子変異情報が臨床の現場にうまく還元できる可能性を示した。さらに今回の研究では、本症における突然死リスク、塞栓症リスク、そして心不全に進展しやすいリスク因子の同定に成功し、肥大型心筋症の診療に極めて重要な知見を発信することができた。
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Report
(6 results)
Research Products
(39 results)
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[Journal Article] Lifelong Clinical Impact of the Presence of Sarcomere Gene Mutation in Japanese Patients With Hypertrophic Cardiomyopathy2020
Author(s)
Nakashima Y, Kubo T, Sugiuta K, Ochi Y, Takahashi A, Baba Y, Hirota T, Yamasaki N, Kimura A, Doi YL, Kitaoka H.
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Journal Title
Circulation Journal
Volume: 84
Issue: 10
Pages: 1846-1853
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2020-09-25
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sudden cardiac death-related events of hypertrophic cardiomyopathy in a regional Japanese cohort -Results from Kochi RYOMA Study.2020
Author(s)
Kubo T, Baba Y, Ochi Y, Takahashi A, Hirota T, Yamasaki N, Hamashige N, Yamamoto K, Kondo F, Bando K, Yamada E, Furuno T, Yabe T, Doi YL, Kitaoka H.
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Journal Title
Circ Rep
Volume: 2
Issue: 8
Pages: 433-439
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical Profile of Thromboembolic Events in Patients With Hypertrophic Cardiomyopathy in a Regional Japanese Cohort ― Results From Kochi RYOMA Study ―2019
Author(s)
Hirota T, Kubo T, Baba Y, Ochi Y, Takahashi A, Yamasaki N, Hamashige N, Yamamoto K, Kondo F, Bando K, Yamada E, Furuno T, Yabe T, Doi YL, Kitaoka H.
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Journal Title
Circulation Journal
Volume: 83
Issue: 8
Pages: 1747-1754
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2019-07-25
Related Report
Peer Reviewed / Open Access
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[Journal Article] Patients’ Characteristics and Clinical Course of Hypertrophic Cardiomyopathy in a Regional Japanese Cohort ― Results From Kochi RYOMA Study ―2018
Author(s)
Kubo T, Hirota T, Baba Y, Ochi Y, Takahashi A, Yamasaki N, Hamashige N, Yamamoto K, Kondo F, Bando K, Yamada E, Furuno T, Yabe T, Doi YL, Kitaoka H.
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Journal Title
Circulation Journal
Volume: 82
Issue: 3
Pages: 824-830
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed / Open Access
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[Journal Article] International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM).2018
Author(s)
O'Mahony C, Jichi F, Ommen SR, Christiaans I, Cecchi F, Olivotto I, Kitaoka H, Gotsman I, Carr-White G, Mogensen J, Antoniades L, Mohiddin SA, Maurer MS, Tang HC, Geske JB, Siontis KC, Mahmoud KD, Vermeer A, Wilde A, Favalli V, Guttmann OP, Gallego-Delgado M, Dominguez F, Tanini I, Kubo T, Elliott PM.
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Journal Title
Circulation
Volume: 137
Issue: 10
Pages: 1015-1023
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy.2017
Author(s)
Kubo T, Ochi Y, Baba Y, Hirota T, Tanioka K, Yamasaki N, Yoshimitsu M, Higuchi K, Takenaka T, Nakajima K, Togawa T, Tsukimura T, Sano S, Tei C, Sakuraba H, Kitaoka H.
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Journal Title
J Cardiol.
Volume: 69
Issue: 1
Pages: 302-307
DOI
Related Report
Peer Reviewed / Open Access
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