Research of the factors to contribute to the onset and the prognosis of hypertrophic cardiomyopathy by the registration study

• Project/Area Number: 26460742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Epidemiology and preventive medicine
• Research Institution: Kanazawa University
• Principal Investigator: FUJINO Noboru 金沢大学, 保健学系, 准教授 (40361993)
• Co-Investigator(Kenkyū-buntansha): 林 研至 金沢大学, 附属病院, 助教 (00422642) ; 山岸 正和 金沢大学, 医学系, 教授 (70393238)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肥大型心筋症 / 遺伝子解析 / 不整脈 / 突然死 / 心不全 / 収縮不全 / 次世代シーケンス / 倫理

Outline of Final Research Achievements

We could register 77 cases of hypertrophic cardiomyopathy (HCM). Whole exome sequencing (WES) was performed on seven relatives from a large HCM family with a clear HCM phenotype (five clinically affected and two unaffected) in our registry study. WES detected 60020 rare variants in the large HCM family. After genotype-phenotype matching, 13 putative variants remained. Using combined annotation dependent depletion (CADD) score and high heart expression (HHE) gene data, the number of candidates was reduced to one, a variant in the myosin essential light chain, p.Arg94His.

Research Products

• [Journal Article] Hypokalemia and the Disappearance of Giant Negative T Waves (2016)
  • Author(s): Konno T, Hayashi K, Fujino N, Yamagishi M
  • Journal Title: Internal Medicine Volume: 55 Issue: 5 Pages: 545-546
  • DOI: 10.2169/internalmedicine.55.5770
  • NAID: 130005132630
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of Electrocardiographic Voltage to Determine Myocardial Fibrosis in Hypertrophic Cardiomyopathy. (2016)
  • Author(s): Konno T, Nagata Y, Teramoto R, Fujino N, Nomura A, Tada H, Sakata K, Furusho H, Takamura M, Nakamura H, Kawashiri MA, Yamagishi M, Hayashi K.
  • Journal Title: Am J Cardiol. Volume: 117 Issue: 3 Pages: 443-449
  • DOI: 10.1016/j.amjcard.2015.11.015
  • Peer Reviewed / Open Access
• [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] Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy. (2015)
  • Author(s): Konno T, Hayashi K, Fujino N, Oka R, Nomura A, Nagata Y, Hodatsu A, Sakata K, Furusho H, Takamura M, Nakamura H, Kawashiri MA, Yamagishi M.
  • Journal Title: J Cardiovasc Electrophysiol. Volume: 26 Issue: 10 Pages: 1081-1087
  • DOI: 10.1111/jce.12742
  • Peer Reviewed / Open Access
• [Journal Article] Right ventricular hypertrophy is associated with cardiovascular events in hypertrophic cardiomyopathy: evidence from study with magnetic resonance imaging. (2015)
  • Author(s): Nagata Y, Konno T, Fujino N, Hodatsu A, Nomura A, Hayashi K, Nakamura H, Kawashiri MA, Yamagishi M.
  • Journal Title: Can J Cardiol. Volume: 31 Issue: 6 Pages: 702-708
  • DOI: 10.1016/j.cjca.2014.12.036
  • 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] Fragmented QRS Predicts Heart Failure Progression in Patients With Hypertrophic Cardiomyopathy (2014)
  • Author(s): Nomura A, Konno T, Fujita T, Tanaka Y, Nagata Y, Tsuda T, Hodatsu A, Sakata K, Nakamura H, Kawashiri MA, Fujino N, Yamagishi M, Hayashi K.
  • Journal Title: Circulation Journal Volume: 79 Issue: 1 Pages: 136-143
  • DOI: 10.1253/circj.CJ-14-0822
  • NAID: 130004704014
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Compound heterozygosity deteriorates phenotypes of hypertrophic cardiomyopathy with founder MYBPC3 mutation: evidence from patients and zebrafish models. (2014)
  • Author(s): Hodatsu A, Konno T, Hayashi K, Funada A, Fujita T, Nagata Y, Fujino N, Kawashiri MA, Yamagishi M.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 307 Issue: 11 Pages: 1594-604
  • DOI: 10.1152/ajpheart.00637.2013
  • Peer Reviewed
• [Journal Article] High sensitivity of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens in hypertrophic cardiomyopathy. (2014)
  • Author(s): Konno T，Hayashi K，Fujino N，Nagata Y，Hodatsu A，Masuta E，Sakata K，Nakamura H，Kawashiri M，Yamagishi M.
  • Journal Title: PLoS One. Volume: 9 Issue: 7 Pages: e101465-e101465
  • DOI: 10.1371/journal.pone.0101465
  • NAID: 120006460361
  • Peer Reviewed / Open Access
• [Journal Article] Left ventricular apical aneurysm and systolic dysfunction in hypertrophic cardiomyopathy. (2014)
  • Author(s): Fujino N, Konno T, Yamagishi M, Hayashi K.
  • Journal Title: J Cardiol Volume: 64 Issue: 4 Pages: 253-5
  • DOI: 10.1016/j.jjcc.2014.04.009
  • Peer Reviewed / Open Access
• [Presentation] Effect of olmesartan alone, and in combination with azelnidipine in the control of hypertension and plasma B-type natriuretic peptide levels (2016)
  • Author(s): Fujino N, Hayashi K, Sakata K, Konno T, Tsuda T, Nagata Y, Teramoto R, Nomura A, Tanaka Y, Yamagishi M
  • Organizer: 21st World Congress on Heart Disiease
  • Place of Presentation: ボストン（アメリカ合衆国）
  • Year and Date: 2016-07-30
  • Int'l Joint Research
• [Presentation] Targeted Sequencing Panel Focusing on 21 Cardiomyopathy-associated Genes Efficiently Identifies Disease-causing Variants in Patients with Hypertrophic Cardiomyopathy (2016)
  • Author(s): Ryota Teramoto Noboru Fujino , Hayato Tada , Tetsuo Konno , Kenshi Hayashi , Masaaki Kawashiri , Masakazu Yamagishi
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Current Perspectives in Common and Rare Variant Association Study for Plasma Lipids and Coronary Artery Disease (2014)
  • Author(s): 多田隼人、今野哲雄、林研至、川尻剛照、藤野陽、山岸正和
  • Organizer: 第62回日本心臓病学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2014-09-27
  • Invited