Research of the hypertrophic and dilated cardiomyopathy : From both approaches of the molecular genetics and the clinical functional analysis

• Project/Area Number: 19590807
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: FUJINO Noboru Kanazawa University, 保健学系, 准教授 (40361993)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 心臓病態学 / 遺伝学 / 遺伝子 / 心筋症 / 肥大型心筋症 / 拡張型心筋症 / 遺伝子解析 / 遺伝子変異 / 非対称性中隔肥厚 / フォスフォランバン遺伝子 / 遺伝子導入

Research Abstract

548の心筋症家系(肥大型心筋症400家系、拡張型心筋症148家系)に関して、発端者ならびにその家族の臨床所見および遺伝子変異を解析した。肥大型心筋症の遺伝子変異保因者臨床像について特に左室収縮機能に着目した所、ミオシン群75例(心筋ベータミオシン重鎖遺伝子およびミオシン結合蛋白C遺伝子)とトロポニン群75例(心筋トロポニンT遺伝子および心筋トロポニンI遺伝子)では、収縮不全(左室駆出率50%未満)の合併に違いが認められた。40歳以上の症例における収縮不全発症率について、トロポニン群ではミオシン群と比較して有意に発症率が高いことが示された。

Research Products

• [Journal Article] Impact of anti-apoptotic and-oxidative effects of bone marrow mesenchymal stem cells with transient overexpression of heme oxygenase-1 on myocardial ischemia. (2010)
  • Author(s): Tsubokawa T, Yagi K, Nakanishi C, Zuka M, Nohara A, Ino H, Fujino N, Konno T, Kawashiri M, Ishibashi-Ueda H, Nagaya N, Yamagishi M
  • Journal Title: American Journal of Physiology-Heart and Circulatory Physiology (in press)
  • Peer Reviewed
• [Journal Article] 循環器疾患発症の分子機序(心筋症-1、肥大型心筋症) (2010)
  • Author(s): 藤野陽、今野哲雄、井野秀一、山岸正和
  • Journal Title: 循環器疾患のサイエンス Pages: 105-110
• [Journal Article] Impact of anti-apoptotic and-oxidative effects of bone marrow mesenchymal stem cells with transient overexpression of heme oxygenase-1 on myocardial ischemia (2010)
  • Author(s): Tsubokawa T, Fujino N, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] 循環器疾患発症の分子機序(心筋症-1、肥大型心筋症) (2010)
  • Author(s): 藤野陽、山岸正和, ら
  • Journal Title: 循環器疾患のサイエンス Pages: 105-110
• [Journal Article] Long QT syndrome and associated gene mutation carriers in Japanese children: results from ECG screening examinations. (2009)
  • Author(s): Hayashi K, Fujino N, Uchiyama K, Ino H, Sakata K, Konno T, Masuta E, Funada A, Sakamoto Y, Tsubokawa T, Nakashima K, Liu L, Higashida H, Hiramaru Y, Shimizu M, Yamagishi M.
  • Journal Title: Clin Sci (Lond) 117 Pages: 415-424
  • Peer Reviewed
• [Journal Article] Impact of QT variables on clinical outcome of genotyped hypertrophic cardiomyopathy. (2009)
  • Author(s): Uchiyama K, Hayashi K, Fujino N, Konno T, Sakamoto Y, Sakata K, Kawashiri MA, Ino H, Yamagishi M.
  • Journal Title: Ann Noninvasive Electrocardiol 14 Pages: 65-71
  • Peer Reviewed
• [Journal Article] Long QT syndrome and associated gene mutation carriers in Japanese children : results from ECG screening examinations (2009)
  • Author(s): Hayashi K, Fujino N, et al.
  • Journal Title: Clin Sci(Lond) 117 Pages: 415-424
  • Peer Reviewed
• [Journal Article] Exercise-induced systolic dysfunction in patients with non-obstructive hypertrophic cardiomyopathy and mutations in the cardiac troponin genes. (2008)
  • Author(s): Sakata K, Ino H, Fujino N, Nagata M, Uchiyama K, Hayashi K, Konno T, Inoue M, Kato H, Sakamoto Y, Tsubokawa T, Yamagishi M.
  • Journal Title: Heart 94 Pages: 1282-1287
  • Peer Reviewed
• [Journal Article] Takotsubo cardiomyopathy with marked ST-segment elevation and electrical alternans complicated with hyperglycemic hyperosmolar state. (2008)
  • Author(s): Oe K, Mori K, Otsuji M, Konno T, Fujino N, Yamagishi M.
  • Journal Title: Int Heart J 49 Pages: 629-35
  • NAID: 130000069071
  • Peer Reviewed
• [Journal Article] A novel beta-myosin heavy chain gene mutation, p. Met531Arg, identified in isolated left ventricular non-compaction in humans, results in left ventricular hypertrophy that progresses to dilation in a mouse model. (2008)
  • Author(s): Kaneda T, Naruse C, Kawashima A, Fujino N, Oshima T, Namura M, Nunoda S, Mori S, Konno T, Ino H, Yamagishi M, Asano M.
  • Journal Title: Clin Sci(Lond) 114 Pages: 431-40
  • Peer Reviewed
• [Journal Article] A novel beta-myosin heavy chain gene mutation, p. Met531Arg, identified in isolated left ventricular non-compaction in humans, results in left ventricular hypertrophy that progresses to dilation in a mouse model (2008)
  • Author(s): Kaneda T, Fujino N, et al.
  • Journal Title: Clin Sci (Lond) 114 Pages: 431-440
  • Peer Reviewed
• [Journal Article] Exercise-induced systolic dysfunction in patients with non-obstructive hypertrophic cardiomyopathy and mutations in the cardiac troponin genes (2008)
  • Author(s): Sakata K, Fujino N, et al.
  • Journal Title: Heart 94 Pages: 1282-1287
  • Peer Reviewed
• [Journal Article] サルコメア遺伝子変異と肥大型心筋症 (2008)
  • Author(s): 藤野陽, 村本明彦, 山岸正和
  • Journal Title: 循環器科 63 Pages: 548-552
• [Journal Article] A novel beta-myosin heavy chain gene mutation,p.Met531Arg,identified in isolated left ventricular non-compaction in humans,results in left ventricular hypertrophy that progresses to dilation in a mouse model (2008)
  • Author(s): Kaneda T, Fujino N, et. al.
  • Journal Title: Clin Sci(Lond) 114 Pages: 431-440
  • Peer Reviewed
• [Journal Article] Exercise-induced systolic dysfunction in patients with non-obstructive hypertrophic cardiomyopathy and mutations in the cardiac troponin genes (2007)
  • Author(s): Sakata K, Fujino N, et. al.
  • Journal Title: Heart (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Differences in the diagnostic value of various criteria of negative T waves for hypertrophic cardiomyopathy based on a molecular genetic diagnosis (2007)
  • Author(s): Konno T, Fujino N, et. al.
  • Journal Title: Clin Sci(Lond) 112 Pages: 577-582
  • Peer Reviewed
• [Presentation] Genetic Analysis and Hypertrophic Cardiomyopathy : Case Presentation (2010)
  • Author(s): Fujino N, Yamagishi M, et al.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 国立京都国際会館、グランドプリンスホテル京都(京都府)
  • Year and Date: 2010-03-06
• [Presentation] 会長特別企画:フォーカスセッション2「家族性心疾患」:Genetic Analysis and Hypertrophic Cardiomyopathy: Case Presentation. (2010)
  • Author(s): Fujino N, Ino H, Hayashi H, Uchiyama K, Masuta E, Sakamoto Y, Tsubokawa T, Funada A, Muramoto A, Yokawa J, Yamagishi M
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 国立京都国際会館, グランドプリンスホテル京都(京都府)
• [Presentation] Significance of Genetic Analysis in Hypertrophic Cardiomyopathy: Comparison of Development to End-Stage Phase in Thick and Thin Filament Mutations Carriers. (2010)
  • Author(s): Fujino N, Ino H, Hayashi H, Uchiyama K, Masuta E, Sakamoto Y, Tsubokawa T, Funada A, Muramoto A, Yokawa J, Yamagishi M.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 国立京都国際会館, グランドプリンスホテル京都(京都府)
• [Presentation] Impact of Genetic Screening on the Development to End-Stage Phase in Hypertrophic Cardiomyopathy: From the Comparison of Clinical Course in Carriers with Thick Filament Mutations and Thin Filament Mutations. (2009)
  • Author(s): Fujino N, Ino H, Hayashi H, Uchiyama K, Masuta E, Sakamoto Y, Tsubokawa T, Funada A, Muramoto A, Yokawa J, Yamagishi M.
  • Organizer: American Heart Association's scientific sessions
  • Place of Presentation: オーランドコンベンションセンター, ハーバード大学医学部遺伝学部門(USA)
• [Presentation] シンポジウム8「慢性心不全のガイドラインを検証する」S-8-6「心筋症に伴う慢性心不全の予後: Genotyped症例での検討」. (2009)
  • Author(s): 藤野陽、井野秀一、舟田晃、舛田英一、村本明彦、山岸正和
  • Organizer: 第57回日本心臓病学会学術集会
  • Place of Presentation: ロイトン札幌, ウェルシティ札幌(北海道)
• [Presentation] Comparison of phenotype of hypertrophic cardiomyopathy associated with a calcium regulating gene and a sarcomere gene. (2009)
  • Author(s): Fujino N, Ino H, Hayashi K, Uchiyama K, Masuta E, Sakamoto Y, Tsubokawa T, Funada A, Muramoto A, Yamagishi M.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪国際会議場, リーガロイヤルホテル大阪(大阪府)
• [Presentation] Symposium 7 Proarrhythmic risk of drugs and their evaluation: Impact of combined risk factors on reduction of repolarization reserve associated with drug-induced abnormal QT prolongation and Torsade de Pointes. (2009)
  • Author(s): Hayashi K, Sakamoto Y, Fujino N, Uchiyama K, Ino H, Masuta E, Funada A, Tsubokawa T, Muramoto A, Yamagishi M.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪国際会議場, リーガロイヤルホテル大阪(大阪府)
• [Presentation] Impact of 123I-BMIPP on Prognosis of Nonobstructive Hypertrophic Cardiomyopathy : From 10 Years Follow-up Data (2008)
  • Author(s): Fujino N, et al.
  • Organizer: American Society of Nuclear Cardiology
  • Place of Presentation: 米国, ボストン
  • Year and Date: 2008-09-11
• [Presentation] Impact of Missense Mutations in Cardiac Ryanodine Receptor Gene as a Cause of Hypertrophic Cardiomyopathy: A New Insight From Ca Handling (2008)
  • Author(s): Fujino N, et. al.
  • Organizer: 第72回日本循環器学会学術集会(シンポジウム)
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-20
• [Presentation] Impact of 123I-BMIPP on prognosis of nonobstructive hypertrophic cardiomyopathy: from 10 years follow-up data. (2008)
  • Author(s): Fujino N, Ino H, Nakajima K, Yamagishi M.
  • Organizer: American Society of Nuclear Cardiology, 2008
  • Place of Presentation: John B. Hynes Veterans Memorial Convention Center(USA).