Molecular pathogenesis mechanism of idiopatic ventricular fibrillation related to Semapolin 3A gene

• Project/Area Number: 26461130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hiroshima University
• Principal Investigator: Nakano Yukiko 広島大学, 病院, 講師 (10397911)
• Co-Investigator(Kenkyū-buntansha): 越智 秀典 広島大学, 医歯薬保健学研究院(医), 講師 (10415119)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: セマフォリン3A / 特発性心室細動 / 一塩基多型 / ブルガダ症候群 / 心室細動 / 遺伝子多型

Outline of Final Research Achievements

We reported that Semapholin 3A (SEMA3A) was related to occurrence of ideoventricular ventricular fibrillation (IVF). The other SNPs having an interaction with SEMA3AI334V and likely to develop VF have not found in SEMA3A tag SNP and causative genes in Brugada syndrome. There was no difference in receptor binding assay and dimer formation between SEMA3I334V and wild type. We have to continue to consider relationship between SEMA3A and pathogenesis of arrhythmia.

Research Products

• [Journal Article] Genotype-phenotype correlation of SCN5A mutation for clinical and electrocardiographic characteristics of probands with Brugada syndrome: Japanese Multicenter Registry. (2017)
  • Author(s): Yamagata K, Horie M, et al.
  • Journal Title: Circulation Volume: 印刷中 Issue: 23 Pages: 0-0
  • DOI: 10.1161/circulationaha.117.027983
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Arrhtyhmia risk and β-blocker therapy in pregnant women with long QT syndrome. (2017)
  • Author(s): Ishibashi K, Horie M, et al.
  • Journal Title: Heart Volume: 印刷中 Issue: 17 Pages: 0-0
  • DOI: 10.1136/heartjnl-2016-310617
  • Peer Reviewed / Open Access
• [Journal Article] DNA damage in lymphocytes induced by cardiac CT and comparison with physical exposure parameters. (2017)
  • Author(s): Fukumoto W, Ishida M, Sakai C, Tashiro S, Ishida T, Nakano Y, Tatsugami F, Awai K.
  • Journal Title: European Radiology Volume: 27 Issue: 4 Pages: 1660-1666
  • DOI: 10.1007/s00330-016-4519-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Variants in the SCN5A Promoter Associated With Various Arrhythmia Phenotypes. (2016)
  • Author(s): Yagihara N,Minamino T,33名中28番
  • Journal Title: J Am Heart Assoc. Volume: 19 Issue: 9 Pages: 644-650
  • DOI: 10.1161/jaha.116.003644
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese (2016)
  • Author(s): Nakano Y, Ochi H, Onohara Y, Sairaku A, Tokuyama T, Matsumura H, Tomomori S, Amioka M, Hironomobe N, Motoda C, Oda N, Chayama K, Chen CH, Gross ER, Mochly-Rosen D, Kihara Y
  • Journal Title: J Biomed Sci Volume: - Issue: 1 Pages: 89-89
  • DOI: 10.1186/s12929-016-0304-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Risk Stratification of Ventricular Fibrillation in Brugada Syndrome Using Noninvasive Scoring Methods (2016)
  • Author(s): Kawazoe H, Nakano Y, Ochi H, Takagi M, Hayashi Y, Uchimura Y, Tokuyama T, Watanabe Y, Matsumura H, Tomomori S, Sairaku A, Suenari K, Awazu A, Miwa Y, Soejima K, Chayama K, Kihara Y
  • Journal Title: Heart Rhythm Volume: 13(10） Issue: 10 Pages: 1947-54
  • DOI: 10.1016/j.hrthm.2016.07.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Common Variant Near HEY2 Has a Protective Effect on Ventricular Fibrillation Occurrence in Brugada Syndrome by Regulating the Repolarization Current. (2016)
  • Author(s): Nakano Y, Ochi H, Onohara Y, Toshishige M, Tokuyama T, Matsumura H, Kawazoe H, Tomomori S, Sairaku A, Watanabe Y, Ikenaga H, Motoda C, Suenari K, Hayashida Y, Miki D, Oda N, Kishimoto S, Oda N, Yoshida Y, Tashiro S, Chayama K, Kihara Y.
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 9(1) Issue: 1
  • DOI: 10.1161/circep.115.003436
  • Peer Reviewed
• [Journal Article] Who is the operator, that is the question: a multicentre study of catheter ablation of atrial fibrillation (2016)
  • Author(s): Sairaku A, Yoshida Y, Nakano Y, Maeda M, Hirayama H, Hashimoto H, Kihara Y
  • Journal Title: Europace Volume: 18(9) Issue: 9 Pages: 1352-6
  • DOI: 10.1093/europace/euv424
  • Peer Reviewed
• [Journal Article] Increased left atrial pressure in non-heart failure patients with subclinical hypothyroidism and atrial fibrillation (2016)
  • Author(s): Sairaku A, Nakano Y, Uchimura Y, Tokuyama T, Kawazoe H, Watanabe Y, Matsumura H, Kihara Y
  • Journal Title: Endocr Connect Volume: 5(3) Issue: 3 Pages: 101-106
  • DOI: 10.1530/ec-16-0012
  • Peer Reviewed
• [Journal Article] Electrical remodeling of the atrioventricular node caused by persistent atrial fibrillation in humans (2016)
  • Author(s): Sairaku A, Nakano Y, Suenari K, Tokuyama T, Kawazoe H, Matsumura H, Tomomori S, Amioka M, Kihara Y
  • Journal Title: J Cardiovasc Electrophysiol Volume: 27(8) Issue: 1 Pages: 918-22
  • DOI: 10.1093/ehjci/jew039
  • Peer Reviewed / Open Access
• [Journal Article] Don't expect left ventricular reverse remodeling after cardiac resynchronization therapy in patients with systolic heart failure and atrioventricular block: A multicenter study (2016)
  • Author(s): Sairaku A, Yoshida Y, Nakano Y, Hirayama H, Maeda M, Hashimoto H, Kihara Y
  • Journal Title: Int J Cardiol Volume: 221 Pages: 597-600
  • DOI: 10.1016/j.ijcard.2016.06.338
  • Peer Reviewed / Open Access
• [Journal Article] Dexmedetomidine depresses sinoatrial and atrioventricular nodal function without any change in atrial fibrillation inducibility (2016)
  • Author(s): Sairaku A, Nakano Y, Suenari K, Tokuyama T, Kawazoe H, Matsumura H, Tomomori S, Amioka M, Kihara Y.
  • Journal Title: J Cardiovasc Pharmacol Volume: 68(6) Issue: 6 Pages: 473-478
  • DOI: 10.1097/fjc.0000000000000434
  • Peer Reviewed / Open Access
• [Journal Article] Genetics of Long QT syndrome (Review) (2015)
  • Author(s): Nakano Y and Shimizu W
  • Journal Title: Journal of Human Genetics Volume: 74 Issue: 1 Pages: 1-5
  • DOI: 10.1038/jhg.2015.74
  • Peer Reviewed
• [Presentation] Risk Stratification of Ventricular Fibrillation in Brugada Syndrome Using Clinical and Molecular Biological Parameters is useful for Deciding an Optimal Therapeutic Strategy (2017)
  • Author(s): Nakano Y, Kawazoe H, Ochi H, Sairaku A, Tokuyama T, Matsumura H, Tomomori S, Amioka M, Hironobe N, Motoda C, Onohara Y, Chayama K, Kihara Y
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Variants of Aldehyde Dehydrogenase 2 and Alcohol Dehydrogenase Genes are Associated with Atrial Fibrillation (2017)
  • Author(s): Nakano Y, Ochi H, Onohara Y, Sairaku A, Tokuyama T, Matsumura H, Tomomori S, Amioka M, Hironobe N, Motoda C, Oda N, Chayama K, Kihara Y
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Sinus Node Recovery Time and ZFHX3 SNP Minor Allele were Independent Predictors of Atrial Fibrillation Recurrence after Pulmonary Vein Isolation (2017)
  • Author(s): Tomomori S, Nakano Y, Tokuyama T, Sairaku A, Matsumura H, Amioka M, Hironobe N, Kihara Y
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Can NT-pro BNP predict left atrial pressure in patients with persistent atrial fibrillation: Lame duck or smart apple? (2017)
  • Author(s): Amioka M, Sairaku A, Hironobe N, Tomomori S, Matsumura H, Tokuyama T, Nakano Y, Kihara Y
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] A common SCN5A polymorphism H558R modifies cis-allelic expression level of SCN5A by modulating DNA methylation of SCN5A promoters (2017)
  • Author(s): Matumura H, Nakano Y, Sairaku A, Tokuyama T, Tomomori S, Amioka M, Hironobe N, Kihara Y
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Variants Of Aldehyde Dehydrogenase 2 And Alcohol Dehydrogenase Genes Are Associated With Atrial Fibrillation (2016)
  • Author(s): Nakano Y, Ochi H, Tomomori S, Matsumura H, Tokuyama T, Sairaku A, Motoda C, Chayama K, Chen C, Mochly-Rosen D, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] A common SCN5A polymorphism H558R modifies clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters (2016)
  • Author(s): Matsumura H, Nakano Y, Sairaku A, Tokuyama T, Tomomori S, Amioka M, Hironobe N, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] A common genetic variant within SCN10A modulates DNA methylation of SCN5A Promoters (2016)
  • Author(s): Hironobe N, Nakano Y, Tokuyama T, Sairaku A, Matsumura H, Tomomori S, Amioka M, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Risk Stratification of Ventricular Fibrillation in Brugada Syndrome Using Logistic Models of Noninvasive Parameters (2016)
  • Author(s): Nakano Y, Kawazoe H, Ochi H, Takagi M, Tokuyama T, Sairaku A, Matsumura H, Tomomori S, Amioka M, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] A novel approach to tailor heparin dosage during ablation of atrial fibrillation: an assessment of sensitivity to unfractionated heparin (2016)
  • Author(s): Sairaku A, Nakano Y, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Common variant in PITX2 contributes to the pathogenesis of paroxysmal atrial fibrillation by impairing sinus node function and progression of atrial remodeling (2016)
  • Author(s): Tomomori S, Nakano Y, Tokuyama T, Sairaku A, Matsumura H, Amioka M, Hironobe N, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Sinus node recovery time and minor allele of ZFHX3 SNP were independent predictors of atrial fibrillation recurrence after pulmonary vein isolation (2016)
  • Author(s): Tomomori S, Nakano Y, Tokuyama T, Sairaku A, Matsumura H, Amioka M, Hironobe N, Kihara Y
  • Organizer: American Heart Association 2016
  • Place of Presentation: New Orleans,USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Newly Developed Atrial Fibrillation Is an Unfavorable Sign of Anthracycline-induced Cardiomyopathy (2016)
  • Author(s): Amioka M, Sairaku A, Ochi T, Okada T, Asaoku H, Nakano Y, Kihara Y
  • Organizer: European Society of Cardiology 2016
  • Place of Presentation: Roma,Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Predictors of the pulmonary vein isolation responders in terms of left atrial deformation and hemodynamics in patients with atrial fibrillation (2016)
  • Author(s): Suenari K, Tomomori S, Matsumura H, Kawazoe H, Tokuyama T, Sairaku A, Nakano Y, Kihara Y
  • Organizer: European Society of Cardiology 2016
  • Place of Presentation: Roma,Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] SCN5A H558R Polymorphism Counteracts Effects of SCN5A Mutations by Decrease Risk Allele Expression Level (2015)
  • Author(s): Matsumura H, Nakano Y, Suenari K, Tokuyama T, Sairaku A, Kawazoe H, Tomomori S, Kihara Y
  • Organizer: The 88th Scientific Sessions of the American Heart Association 2015
  • Place of Presentation: Orlando,USA
  • Year and Date: 2015-11-08
• [Presentation] Common Variant Near Hey2 as a Protective Modifier of Ventricular Fibrillation in Brugada Syndrome by Modurating QTc Interval (2014)
  • Author(s): Nakano Y, Ochi H, Toshishige M, Tokuyama T, Kawazoe H, Watanabe Y, Matsumura M, Tomomori S, Kishimoto S, Ikenaga H, Oda N, Chayama K, Kihara Y
  • Organizer: The 87th Scientific Sessions of the American Heart Association 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Negative Association of H558r Polymorphism and Ventricular Fibrillation in Patients With Brugada Syndrome (2014)
  • Author(s): Matsumura H, Nakano Y, Toshishige M, Ochi H, Tokuyama T, Watanabe Y, Kawazoe H, Tomomori S, Kishimoto S, Chayama K, Kihara Y
  • Organizer: The 87th Scientific Sessions of the American Heart Association 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Remarks] 不整脈により突然死を起こすブルガダ症候群（ポックリ病）の発症リスクが低減する遺伝子を発見
  • URL: https://www.hiroshima-u.ac.jp/med/news/14582
• [Remarks] [研究成果]不整脈により突然死を起こすブルガダ症候群（ポックリ病）の発症リスクが低減する遺伝子を発見
  • URL: http://www.hiroshima-u.ac.jp/news/show/id/24743/dir_id/28