特発性心室細動の遺伝的成因と臨床像の関係および遺伝子型に基づく個別化治療の構築

• 研究課題/領域番号: 22790696
• 研究種目: 若手研究(B)
• 配分区分: 補助金
• 研究分野: 循環器内科学
• 研究機関: 新潟大学
• 研究代表者: 渡部 裕 新潟大学, 医歯学総合病院, 助教 (10547558)
• 研究期間 (年度): 2010 – 2011
• 研究課題ステータス: 完了 (2011年度)
• 配分額: 3,510千円 (直接経費: 2,700千円、間接経費: 810千円); 2011年度: 2,340千円 (直接経費: 1,800千円、間接経費: 540千円); 2010年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
• キーワード: 不整脈 / 心電図 / 遺伝子 / イオンチャネル / リスクファクター

研究概要

近年注目を集めている早期再分極関連心室細動は臨床像や、機序、遺伝的背景など未解明の点が多い。また突然死予防のためのリスク層別化に必要な臨床像の解明は十分ではない。本研究は、特発性心室細動の臨床像並びに新たな遺伝的背景と不整脈発生の機序を解明した。また臨床象ならびに遺伝子型を考慮した新たな個別化治療のために有用である不整脈発作の危険因子を同定した。

研究成果

• [雑誌論文] The cholesterol paradox in atrial fibrillation (2012)
  • 著者名/発表者名: Watanabe H, Yagihara N, Aizawa Y, Kodama M, Tanabe N, Watanabe T
  • 雑誌名: Circ J
• [雑誌論文] Response to letter regarding article,"electrocardiographic characteristics and scn5a mutations in idiopathic ventricular fibrillation associated with early repolarization" (2012)
  • 著者名/発表者名: Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M,Aizawa Y, Shimizu W, Makita N
  • 雑誌名: Circ Arrhythm Electrophysiol ページ: 60-61
• [雑誌論文] Electrocardiographic abnormalities and risk of complete atrioventricular block (2012)
  • 著者名/発表者名: Watanabe H, Makita N, Tanabe N, Watanabe T, Aizawa Y
  • 雑誌名: Int J Cardiol 巻: 155 ページ: 462-464
• [雑誌論文] Age and sex differences in association of blood lipid levels with incidence of atrial fibrillation (2012)
  • 著者名/発表者名: Watanabe H, Aizawa Y
  • 雑誌名: Circ Arrhythm Electrophysiol 巻: (In press)
• [雑誌論文] A connexin40 mutation associated with a malignant variant of progressive familial heart block type i (2012)
  • 著者名/発表者名: Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W, Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M, Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M
  • 雑誌名: Circ Arrhythm Electrophysiol 巻: 5 ページ: 163-172
  • NAID: 120006985450
• [雑誌論文] Early repolarization and its modification by preexcitation in two patients with intermittent WPW syndrome (2012)
  • 著者名/発表者名: Hasegawa K, Sato A, Watanabe H, Furushima H, Chinushi M, Aizawa Y
  • 雑誌名: Pacing Clin Electrophysiol
• [雑誌論文] Is the coexistence of sustained st-segment elevation and abnormal q waves a risk factor for electrical storm in implanted cardioverter defibrillator patients with structural heart diseases? (2012)
  • 著者名/発表者名: Furushima H, Chinushi M, Iijima K, Hasegawa K, Sato A, Izumi D, Watanabe H, Aizawa Y
  • 雑誌名: Europace 巻: 14 ページ: 675-681
• [雑誌論文] Exercise-related qt interval shortening with a peaked t wave in a healthy boy with a family history of sudden cardiac death (2012)
  • 著者名/発表者名: Chinushi M, Sato A, Iijima K, Suzuki K, Hiroshi F, Izumi D, Watanabe H, Kanae H, Aizawa Y
  • 雑誌名: Pacing Clin Electrophysiol
• [雑誌論文] Electrocardiographic abnormalities and risk of complete atrioventricular block (2012)
  • 著者名/発表者名: Watanabe H, Makita N, et al
  • 雑誌名: Int J Cardiol 巻: 155 号: 3 ページ: 462-464
  • DOI: 10.1016/j.ijcard.2011.12.028
  • 査読あり
• [雑誌論文] The prevalence of early repolarization in wolff-parkinson-white syndrome with a special reference to j waves and the effects of catheter ablation (2011)
  • 著者名/発表者名: Yagihara N, Sato A, Iijima K, Izumi D, Furushima H, Watanabe H, Irie T, Kaneko Y, Kurabayashi M, Chinushi M, Satou M, Aizawa Y
  • 雑誌名: J Electrocardiol
• [雑誌論文] Striking in vivo phenotype of a disease-associated human scn5a mutation producing minimal changes in vitro (2011)
  • 著者名/発表者名: Watanabe H, Yang T, Stroud DM, Lowe JS, Harris L, Atack TC, Wang DW, Hipkens SB, Leake B, Hall L, Kupershmidt S, Chopra N, Magnuson MA, Tanabe N, Knollmann BC, George AL, Jr., Roden DM
  • 雑誌名: Circulation 巻: 124 ページ: 1001-1011
• [雑誌論文] Association between lipid profile and risk of atrial fibrillation (2011)
  • 著者名/発表者名: Watanabe H, Tanabe N, Yagihara N, Watanabe T, Aizawa Y, Kodama M
  • 雑誌名: Circ J 巻: 75 ページ: 2767-2774
• [雑誌論文] Mechanism of antiarrhythmic effects of flecainide in catecholaminergic polymorphic ventricular tachycardia (2011)
  • 著者名/発表者名: Watanabe H, Steele DS, Knollmann BC
  • 雑誌名: Circ Res 巻: 109 ページ: 712-713
• [雑誌論文] Electrocardiographic characteristics and scn5a mutations in idiopathic ventricular fibrillation associated with early repolarization (2011)
  • 著者名/発表者名: Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Shimizu W, Makita N
  • 雑誌名: Circ Arrhythm Electrophysiol 巻: 4 ページ: 874-881
• [雑誌論文] Mechanism underlying catecholaminergic polymorphic ventricular tachycardia and approaches to therapy (2011)
  • 著者名/発表者名: Watanabe H, Knollmann BC
  • 雑誌名: J Electrocardiol 巻: 44 ページ: 650-655
• [雑誌論文] Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (2011)
  • 著者名/発表者名: van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, Shimizu W, Sumitomo N, Fish FA, Bhuiyan ZA, Willems AR, van der Veen MJ, Watanabe H, Laborderie J, Haissaguerre M, Knollmann BC, Wilde AA
  • 雑誌名: J Am Coll Cardiol 巻: 57 ページ: 2244-2254
• [雑誌論文] Analysis of j waves during myocardial ischaemia (2011)
  • 著者名/発表者名: Sato A, Tanabe Y, Chinushi M, Hayashi Y, Yoshida T, Ito E, Izumi D, Iijima K, Yagihara N, Watanabe H, Furushima H, Aizawa Y
  • 雑誌名: Europace
• [雑誌論文] An appropriate defibrillation threshold obtained by the combined connection between two shock leads and icd generator (2011)
  • 著者名/発表者名: Sato A, Chinushi M, Iijima K, Watanabe H, Izumi D, Furushima H, Sonoda K, Hasegawa K, Yagihara N, Aizawa Y
  • 雑誌名: Intern Med 巻: 50 ページ: 2815-2818
  • NAID: 130002130066
• [雑誌論文] Rise in international normalized ratio after a catastrophic earthquake in patients treated with warfarin (2011)
  • 著者名/発表者名: Oda M, Watanabe H, Oda E, Tomita M, Obata H, Ozawa T, Oda Y, Iizuka T, Toba K, Aizawa Y
  • 雑誌名: Int J Cardiol
• [雑誌論文] Preexcitation unmasks j waves : 2 cases (2011)
  • 著者名/発表者名: Nagao S, Hayashi Y, Yagihara N, Sato A, Watanabe H, Furushima H, Chinushi M, Aizawa Y
  • 雑誌名: J Electrocardiol 巻: 44 ページ: 359-362
• [雑誌論文] Is the coexistence of sustained st-segment elevation and abnormal q waves a risk factor for electrical storm in implanted cardioverter defibrillator patients with structural heart diseases? (2011)
  • 著者名/発表者名: Furushima H, Chinushi M, Iijima K, Hasegawa K, Sato A, Izumi D, Watanabe H, Aizawa Y
  • 雑誌名: Europace
• [雑誌論文] Suppression of storms of ventricular tachycardia by epicardial ablation of isolated delayed potential in noncompaction cardiomyopathy (2011)
  • 著者名/発表者名: Chinushi M, Iijima K, Furushima H, Izumi D, Sato A, Yagihara N, Hasegawa K, Watanabe H, Soejima K, Aizawa Y
  • 雑誌名: Pacing Clin Electrophysiol
• [雑誌論文] Informatic and functional approaches to identifying a regulatory region for the cardiac sodium channel (2011)
  • 著者名/発表者名: Atack TC, Myers Stroud D, Watanabe H, Yang T, Hall L, Hipkens SB, Lowe JS, Leake B, Magnuson MA, Yang P, Roden DM
  • 雑誌名: Circ Res 巻: 109 ページ: 38-46
• [雑誌論文] Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated with Early Repolarization (2011)
  • 著者名/発表者名: Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Shimizu W, Makita N
  • 雑誌名: Circ Arrhythm Electrophysiol 巻: 4 号: 6 ページ: 874-881
  • DOI: 10.1161/circep.111.963983
  • 査読あり
• [雑誌論文] Mechanism of antiarrhythmic effects of flecainide in catecholaminergic polymorphic ventricular tachycardia (2011)
  • 著者名/発表者名: 渡部裕
  • 雑誌名: Circulation Research 巻: 109 号: 6 ページ: 712-713
  • DOI: 10.1161/circresaha.111.251322
  • 査読あり
• [雑誌論文] High prevalence of early repolarization in short QT syndrome (2010)
  • 著者名/発表者名: 渡部裕
  • 雑誌名: Heart Rhythm 巻: 4 ページ: 647-652
  • 査読あり
• [雑誌論文] ガイドラインに基づく不整脈症例の診療 (2010)
  • 著者名/発表者名: 渡部裕
  • 雑誌名: 総合臨床 巻: 2010年増刊 ページ: 726-729
• [学会発表] Clinical, Electrocardiographic, and Genetic Characteristics of Patients with Idiopathic Ventricular Fibrillation associated with Early Repolarization (2011)
  • 著者名/発表者名: 渡部裕
  • 学会等名: American Heart Association Scientific Session
  • 発表場所: アメリカ・オーランド
  • 年月日: 2011-11-13
• [学会発表] Short QT syndromeとJ波・早期再分極 (2011)
  • 著者名/発表者名: 渡部裕
  • 学会等名: 第46回理論心電図研究会
  • 発表場所: 博多(招待講演)
  • 年月日: 2011-09-20
• [学会発表] Short QT syndromeにおける早期再分極 (2011)
  • 著者名/発表者名: 渡部裕
  • 学会等名: 第26回犬山不整脈カンファランス
  • 発表場所: 名古屋(招待講演)
  • 年月日: 2011-08-20
• [学会発表] Effects of Flecainide in Genotype-negative Catecholaminergic Polymorphic Ventricular Tachycardia (2011)
  • 著者名/発表者名: 渡部裕
  • 学会等名: Annual Meeting of Heart Rhythm Society
  • 発表場所: サンフランシスコ
  • 年月日: 2011-05-05
• [学会発表] Mechanism underlying Catecholaminergic Polymorphic Ventricular Tachycardia and approaches to therapy (2011)
  • 著者名/発表者名: 渡部裕
  • 学会等名: Annual Meeting of International Society for Computerized Electrocardiology
  • 発表場所: サンノゼ(招待講演)
  • 年月日: 2011-04-14
• [学会発表] Ventricular arrhythmia ; Acute and long term response to drugs (2010)
  • 著者名/発表者名: 渡部裕
  • 学会等名: XIV International Symposium on Progress in Clinical Pacing
  • 発表場所: イタリア・ローマ(招待講演)
  • 年月日: 2010-12-02
• [学会発表] Not so innocent : "bystander" accessory subunits and arrhythmogenesis (2010)
  • 著者名/発表者名: 渡部裕
  • 学会等名: ヨーロッパ心臓病学会総会
  • 発表場所: スペイン・バルセロナ(招待講演)
  • 年月日: 2010-08-31
• [学会発表] Clinical, Electrocardiographic, and Genetic Characteristics of Patients with Idiopathic Ventricular Fibrillation associated with Early Repolarization
  • 著者名/発表者名: 渡部裕
  • 学会等名: AHA Scientific Sessions 2011
• [学会発表] Effects of Flecainide in Genotype-negative Catecholaminergic Polymorphic Ventricular Tachycardia
  • 著者名/発表者名: 渡部裕
  • 学会等名: Heart Rhythm 2011
• [学会発表] Electrocardiographic risk factors for complete atrioventric ular block
  • 著者名/発表者名: Watanabe H, Watanabe T, Tanabe N, Ai zawa Y, Makita N
  • 学会等名: The Niigata Preventive Med icine Study. AHA Scientific Sessions 2010