Analysis of the pathogenesis of cardiac Na channelopathies

• Project/Area Number: 21790720
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MAKIYAMA Takeru Kyoto University, 医学研究科, 助教 (30528302)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 不整脈 / 分子心臓病態学 / イオンチャネル

Research Abstract

Mutations in SCN5A gene, encoding cardiac Na channels, are reported to cause a variety of arrhythmias. We performed genetic screening on sudden infant death syndrome (SIDS) and clarified that SCN5A mutations are prevalent in Japanese infants with life threatening arrhythmias, in addition, not only SCN5A gain-of-function type modulation (Long-QT syndrome type 3, but also loss-of-function (Brugada syndrome) may be a pathogenic basis of SIDS. Furthemore, we analysed TCAP gene, a member of Z-disk proteins which associate with the cardiac Na channels, on patients with inherited arrhythmias. The mutation might be associated with cardiac arrhythmias by modulating Na currents.

Research Products

• [Journal Article] A novel KCM2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil Syndrome. (2011)
  • Author(s): Doi T, Makiyama T, Morimoto T, Haruna Y, Tsuji K, Akao M, Takahashi Y, Kimura T, Horie M.
  • Journal Title: Circulation Cardiovascular Genetics.
  • Peer Reviewed
• [Journal Article] Novel KCNE5 variants are associated with Brugada syndrome and idiopathic ventricular fibrillation. (2011)
  • Author(s): Ohno S, Zankov D, Ding W, Makiyama T, Doi T, Shizuta S, Itoh H, Nishio Y, Hattori T, Matsuura H, Horie M.
  • Journal Title: Circulation Arrhythmia and Electrophysiol.
  • Peer Reviewed
• [Journal Article] Risk Determinants in Individuals With a Spontaneous Type 1 Brugada ECG. (2011)
  • Author(s): Miyamoto A, Hayashi H, Makiyama T, Yoshino T, Mizusawa Y, Sugimoto Y, Ito M, Xue JQ, Murakami Y, Horie M.
  • Journal Title: Circ J. 75(4) Pages: 1623-9
  • NAID: 10028103115
  • Peer Reviewed
• [Journal Article] A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome (2011)
  • Author(s): Doi T, Makiyama T, et al.
  • Journal Title: Circulation Cardiovascular Genetics Volume: (掲載確定)
  • Peer Reviewed
• [Journal Article] Novel KCNE5 variants are associated with Brugada syndrome and idiopathic ventricular fibrillation (2011)
  • Author(s): Ohno S, Makiyama T, et al.
  • Journal Title: Circulation Arrhythmia and Electrophysiology Volume: (掲載確定)
  • Peer Reviewed
• [Journal Article] Risk Determinants in Individuals With a Spontaneous Type 1 Brugada ECG (2011)
  • Author(s): Miyamoto S, Makiyama T, et al.
  • Journal Title: Circulation Journal Volume: (掲載確定)
  • NAID: 10028103115
  • Peer Reviewed
• [Journal Article] Atrioventricular block-induced Torsades de Pointes with clinical and molecular backgrounds similar to congenital long QT syndrome. (2010)
  • Author(s): Oka Y, Itoh H, Ding WG, Shimizu W, Makiyama T, Ohno S, Nishio Y, Sakaguchi T, Miyamoto A, Kawamura M, Matsuura H, Horie M.
  • Journal Title: Circ J. 25;74(12) Pages: 2562-71
  • NAID: 10027424141
  • Peer Reviewed
• [Journal Article] Heart rate-dependent variability of cardiac events in type 2 congenital long-QT syndrome. (2010)
  • Author(s): Nagaoka I, Shimizu W, Mizusawa Y, Sakaguchi T, Itoh H, Ohno S, Makiyama T, Yamagata K, Makimoto H, Miyamoto Y, Kamakura S, Horie M.
  • Journal Title: Europace. 12(11)
  • Peer Reviewed
• [Journal Article] Long QT syndrome with compound mutations is associated with a more severe phenotype : a Japanese multicenter study. (2010)
  • Author(s): Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Ohno S, Makiyama T, Akao M, Ai T, Noda T, Miyazaki A, Miyamoto Y, Yamagishi M, Kamakura S, Horie M.
  • Journal Title: Heart Rhythm. 7(10) Pages: 1411-1418
  • Peer Reviewed
• [Journal Article] High prevalence of early repolarization in short QT syndrome. (2010)
  • Author(s): Watanabe H, Makiyama T, Koyama T, Kannankeril PJ, Seto S, Okamura K, Oda H, Itoh H, Okada M, Tanabe N, Yagihara N, Kamakura S, Horie M, Aizawa Y, Shimizu W.
  • Journal Title: Heart Rhythm. 7(5) Pages: 647-52
  • Peer Reviewed
• [Journal Article] 堀江稔家族性ベースメーカ植込み症例における遺伝的背景の検討-心臓Na+チャネル病 (2010)
  • Author(s): 牧山武, 静田聡, 赤尾昌治, 木村剛
  • Journal Title: Lamin A/C遺伝子関連心筋症-心電図 30 Pages: 201-209
  • Peer Reviewed
• [Journal Article] A novel SCN5A mutation associated with the linker between III and IV domains of Na (v) 1.5 in a neonate with fatal long QT syndrome. (2010)
  • Author(s): Yamamura K, Muneuchi J, Uike K, Ikeda K, Inoue H, Takahata Y, Shiokawa Y, Yoshikane Y, Makiyama T, Horie M, Hara T.
  • Journal Title: Int J Cardiol. 5;145(1) Pages: 61-64
  • Peer Reviewed
• [Journal Article] 家族性ベースメーカ植込み症例における遺伝的背景の検討-心臓Na+チャネル病、Lamin A/C遺伝子関連心筋症- (2010)
  • Author(s): 牧山武, 静田聡, 赤尾昌治, 木村剛, 堀江稔
  • Journal Title: 心電図 Volume: 30 Pages: 201-209
• [Journal Article] Long QT syndrome with compound mutations is associated with a more severe phenotype : a Japanese multicenter study (2010)
  • Author(s): Itoh H, Makiyama T, et al.
  • Journal Title: Heart Rhythm Volume: 7 Pages: 1411-8
  • Peer Reviewed
• [Journal Article] High prevalence of early repolarization in short QT syndrome (2010)
  • Author(s): Watanabe H, Makiyama T, et al
  • Journal Title: Heart Rhythm Volume: 7 Pages: 647-52
  • Peer Reviewed
• [Journal Article] High prevalence of early repolarization in short QT syndrome. (2010)
  • Author(s): Watanabe H, Makiyama T, et al.
  • Journal Title: Heart Rhythm
  • Peer Reviewed
• [Journal Article] Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. (2009)
  • Author(s): Itoh H, Sakaguchi T, Ding WG, Watanabe E, Watanabe I, Nishio Y, Makiyama T, Ohno S, Akao M, Higashi Y, Zenda N, Kubota T, Mori C, Okajima K, Haruna T, Miyamoto A, Kawamura M, Ishida K, Nagaoka I, Oka Y, Nakazawa Y, Yao T, Jo H, Sugimoto Y, Ashihara T, Hayashi H, Ito M, Imoto K, Matsuura H, Horie M.
  • Journal Title: Circ Arrhythm Electrophysiol. 2(5) Pages: 511-523
  • Peer Reviewed
• [Journal Article] D85N, a KCNE1 polymorphism, is a disease-causing gene variant inlong QT syndrome. (2009)
  • Author(s): Nishio Y, Makiyama T, Itoh H, Sakaguchi T, Ohno S, Gong YZ, Yamamoto S, Ozawa T, Ding WG, Toyoda F, Kawamura M, Akao M, Matsuura H, Kimura T, Kita T, Horie M.
  • Journal Title: J Am Coll Cardiol. 25;54(9) Pages: 812-819
  • Peer Reviewed
• [Journal Article] Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome. (2009)
  • Author(s): Ohno S, Toyoda F, Zankov DP, Yoshida H, Makiyama T, Tsuji K, Honda T, Obayashi K, Ueyama H, Shimizu W, Miyamoto Y, Kamakura S, Matsuura H, Kita T, Horie M.
  • Journal Title: Hum Mutat. 30(4) Pages: 557-563
  • Peer Reviewed
• [Journal Article] Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome. (2009)
  • Author(s): Ohno S, Makiyama T, et al.
  • Journal Title: Human Mutation 30 Pages: 557-563
  • Peer Reviewed
• [Journal Article] D85N, a KCNE1 polymorphism, is a disease-causing gene variant in long QT syndrome. (2009)
  • Author(s): Nishio Y, Makiyama T, et al.
  • Journal Title: The American College of Cardiology 54 Pages: 812-819
  • Peer Reviewed
• [Journal Article] Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. (2009)
  • Author(s): Itoh H, Makiyama T, et al.
  • Journal Title: Circulation Arrhythmia Electrophysiology 2 Pages: 511-523
  • Peer Reviewed
• [Journal Article] A novel SCN5A mutation associated with the linker between III and IV domains of Na(v)1.5 in a neonate with fatal long QT syndrome. (2009)
  • Author(s): Yamamura K, Makiyama T, et al.
  • Journal Title: International Jurnal of Cardiology
  • Peer Reviewed
• [Presentation] Both Gain- and Loss-of-Function Mutations in the Cardiac Na+ Channel Gene, SCN5A, are Associated with Sudden Infant Death Syndrome (SIDS) (2010)
  • Author(s): 牧山武
  • Organizer: APHRS 2010
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2010-10-30
• [Presentation] 心筋症における遺伝的背景の検討(ミオシン重鎖遺伝子解析) (2010)
  • Author(s): 若本陽子
  • Organizer: 第27回日本心電学会学術集会
  • Place of Presentation: 大分
  • Year and Date: 2010-10-08
• [Presentation] KCNE5遺伝子変異からBrugada症候群の性差を考える (2010)
  • Author(s): 大野聖子
  • Organizer: 第27回日本心電学会学術集会
  • Place of Presentation: 大分
  • Year and Date: 2010-10-08
• [Presentation] Inherited VentricularArrhythmic Disorders in Asia : What's New and What's Different from US and Europe? (2010)
  • Author(s): 牧山武
  • Organizer: Heart Rhythm
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-05-15
• [Presentation] Inherited Ventricular Arrhythmic Disorders in Asia : What's New and What's Different from US and Europe? (2010)
  • Author(s): 牧山武
  • Organizer: Heart Rhythm 2010
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-05-15
• [Presentation] Dilated Cardiomyopathy : DCM, Case presentation (2010)
  • Author(s): 牧山武
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-06
• [Presentation] Both Gain- and Loss-of-Function Mutations in the Cardiac Na Channel Gene, SCN5A, are Associated with Sudden Infant Death Syndrome (SIDS) (2010)
  • Author(s): 牧山武
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-05
• [Presentation] Both Gain-andLoss-of-Function Mutations in the Cardiac Na+ Channel Gene, SCN5A, are Associated with Sudden Infant Death Syndrome(SIDS). (2010)
  • Author(s): 牧山武
  • Organizer: 第74回日本循環器学学術集会(Focus session)
  • Place of Presentation: 京都
• [Presentation] Dilated Cardiomyopathy : DCM, Case presentation. (2010)
  • Author(s): 牧山武
  • Organizer: 第74回日本循環器学会学術集会(Focussession)
  • Place of Presentation: 京都
• [Presentation] 家族性ペースメーカー植込み症例における遺伝的背景の検討-心臓Na+チャネル病、lamin A/C関連心筋症- (2009)
  • Author(s): 牧山武
  • Organizer: 第24回日本不整脈学会学術大会/第26回日本心電学会学術集会 合同学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-07-02
• [Presentation] 学術諮問委員会指定トピックス【不整脈の遺伝子診断】:家族性ペースメーカー植込み症例における遺伝的背景の検討-心臓Na+チャネル病、lamin A/C関連心筋症- (2009)
  • Author(s): 牧山武
  • Organizer: 第24回日本不整脈学会学術大会/第26回日本心電学会学術集会合同学術集会
  • Place of Presentation: 京都
• [Presentation] SCN5A and Lamin A/C genemutations are highly prevalent in patients with familial bradyarrhythmic disorders. (2009)
  • Author(s): 牧山武
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
• [Remarks]
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/fuseimyaku/