Searching and analysis of genes causing arrhythmia with pharmacological and non-pharmacological intervention

• Project/Area Number: 25460648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kanazawa University
• Principal Investigator: Ino Hidekazu 金沢大学, 医学系, 協力研究員 (20272966)
• Co-Investigator(Kenkyū-buntansha): FUJINO Noboru 金沢大学, 保健学系, 准教授 (40361993) ; HAYASHI Kenshi 金沢大学, 大学病院, 助教 (00422642)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肥大型心筋症 / 遺伝子解析 / 不整脈 / 突然死 / 非薬物治療 / 非薬物療法

Outline of Final Research Achievements

Hypertrophic cardiomyopathy(HCM) is one of the most frequent diseases causing sudden death especially in young people. We have found that part of the patients with this disease have gene mutations in heart muscle, causing heart function deteriorated, however, the relationship of gene mutation and sudden death mostly by fatal arrhythmia remained unresolved.
Our institution-driven multicenter-prospective trial revealed the presence of gene mutation is associated closely with arrhythmia and heart failure in hypertrophied heart. We detected new mutation with comprehensive analysis using next generation sequencing system in familial HCM without mutation by previous method. . We also analyzed the gene mutations and those function in lone atrial fibrillation, and evaluated the arrhythmogenicity of the mutations by a scoring system. These approaches are anticipated to prevent the sudden death of hypertrophic cardiomyopathy.

Research Products

• [Journal Article] Whole exome sequencing combined with integrated variant annotation prediction identifies a causative myosin essential light chain variant in hypertrophic cardiomyopathy. (2016)
  • Author(s): Nomura A, Tada H, Teramoto R, Konno T, Hodatsu A, Won HH, Kathiresan S, Ino H, Fujino N, Yamagishi M, Hayashi K.
  • Journal Title: J Cardiol. Volume: 2 Issue: 2 Pages: 133-9
  • DOI: 10.1016/j.jjcc.2015.09.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation. (2015)
  • Author(s): Hayashi K, Konno T, Tada H, Tani S, Liu L, Fujino N, Nohara A, Hodatsu A, Tsuda T, Tanaka Y, Kawashiri MA, Ino H, Makita N, Yamagishi M.
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 8 Issue: 5 Pages: 1095-1104
  • DOI: 10.1161/circep.114.002519
  • Peer Reviewed / Open Access
• [Journal Article] Increased extent of myocardial fibrosis in genotyped hypertrophic cardiomyopathy with ventricular tachyarrhythmias. (2014)
  • Author(s): Fujita T, Konno T, Yokawa J, Masuta E, Nagata Y, Fujino N, Funada A, Hodatsu A, Kawashiri MA, Yamagishi M, Hayashi K.
  • Journal Title: J Cardiol. Volume: in press Issue: 1 Pages: 63-68
  • DOI: 10.1016/j.jjcc.2014.10.002
  • Peer Reviewed / Open Access
• [Journal Article] Sarcomere Gene Mutations Are Associated With Increased Cardiovascular Events in Left Ventricular Hypertrophy : Results From Multicenter Registration in Japan. (2013)
  • Author(s): Fujita T, Komuro I (18人中13番目）
  • Journal Title: JACC Heart Fail Volume: 6 Issue: 6 Pages: 459-466
  • DOI: 10.1016/j.jchf.2013.08.007
  • Peer Reviewed