ブルガダ症候群の不整脈発生の概日リズムに関する分子生物学的検討

2017 Fiscal Year Research-status Report

• Project/Area Number: 17K09524
• Research Institution: Keio University
• Principal Investigator: 相澤 義泰 慶應義塾大学, 医学部(信濃町), 特任講師 (20528145)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ブルガダ症候群 / 突然死 / 遺伝子解析 / 日内変動

Outline of Annual Research Achievements

心臓突然死を来す循環器疾患のうち、器質的には異常を認めないが致死的不整脈を来す疾患群が存在する。代表的なブルガダ症候群は若年性突然死の原因となり、特に働き盛りの男性に発症する。約20％にイオンチャネル蛋白の責任遺伝子異常を認めるが未解明な点も多い。申請者はブルガダ症候群で発生する電気的ストームは日内・週内・季節変動することを初めて一連の患者で報告した。ブルガダ症候群の不整脈は夜間睡眠中に起きることが知られているが、不整脈の概日リズムのメカニズムの詳細は未解明である。ブルガダ症候群患者のゲノムを次世代シークエンサーで網羅的に解析し、ひいては概日リズムの分子生物学的背景を解明することを目的として研究を行っている。
これまでにブルガダ症候群患者の遺伝子サンプルは145例集積された。パネルまたはエクソーム解析を行い、SCN5A 12例、、SCN3B 2例、SCN10A 1例、GPD1L １例、デスモゾーム関連遺伝子 6例にrare variantを認めた。変異同定率は15%であった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

症例集積も累計94例と順調であり、遺伝子解析も予定通り施行出来ている。

Strategy for Future Research Activity

またヒトの概日リズムは視交叉上核が時計中枢となり、時計遺伝子（CLOCK, BMAL1, Per, Cry）が調節に関わっているために、心室細動を心筋のチャネル病として捉えるだけでなく、概日リズムの分子生物学的機序と併せて病態を明らかにしていく。

Causes of Carryover

実験試薬の割引により予定額よりも安価で購入できたため。

Research Products

• [Journal Article] Prevalence and clinical characteristics of obstructive- and central-dominant sleep apnea in candidates of catheter ablation for atrial fibrillation in Japan (2018)
  • Author(s): Kohno Takashi、Kimura Takehiro、Fukunaga Koichi、Yamasawa Wakako、Fujisawa Taishi、Fukuoka Ryoma、Nakajima Kazuaki、Kashimura Shin、Kunitomi Akira、Katsumata Yoshinori、Nishiyama Takahiko、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: International Journal of Cardiology Volume: 260 Pages: 99～102
  • DOI: 10.1016/j.ijcard.2018.01.103
  • Peer Reviewed
• [Journal Article] Real‐Time Analysis of the Heart Rate Variability During Incremental Exercise for the Detection of the Ventilatory Threshold (2018)
  • Author(s): Shiraishi Yasuyuki、Katsumata Yoshinori、Sadahiro Taketaro、Azuma Koichiro、Akita Keitaro、Isobe Sarasa、Yashima Fumiaki、Miyamoto Kazutaka、Nishiyama Takahiko、Tamura Yuichi、Kimura Takehiro、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: Journal of the American Heart Association Volume: 7 Pages: e006612～e006612
  • DOI: 10.1161/JAHA.117.006612
  • Peer Reviewed / Open Access
• [Journal Article] Real-world monitoring of direct oral anticoagulants in clinic and hospitalization settings (2017)
  • Author(s): Takatsuki Seiji、Kimura Takehiro、Sugimoto Kazutaka、Misaki Sadaya、Nakajima Kazuaki、Kashimura Shin、Kunitomi Akira、Katsumata Yoshinori、Nishiyama Takahiko、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Fukuda Keiichi
  • Journal Title: SAGE Open Medicine Volume: 5 Pages: 印刷中
  • DOI: 10.1177/2050312117734773
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary Artery Denervation by Determining Targeted Ablation Sites for Treatment of Pulmonary Arterial Hypertension (2017)
  • Author(s): Fujisawa Taishi、Kataoka Masaharu、Kawakami Takashi、Isobe Sarasa、Nakajima Kazuaki、Kunitomi Akira、Kashimura Shin、Katsumata Yoshinori、Nishiyama Takahiko、Kimura Takehiro、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Murata Mitsushige、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: Circulation: Cardiovascular Interventions Volume: 10 Pages: e005812～e005812
  • DOI: 10.1161/CIRCINTERVENTIONS.117.005812
  • Peer Reviewed
• [Journal Article] Mitral isthmus ablation using a circular mapping catheter positioned in the left atrial appendage as a reference for conduction block (2017)
  • Author(s): Nishiyama Takahiko、Kimura Takehiro、Fujisawa Taishi、Nakajima Kazuaki、Kunitomi Akira、Kashimura Shin、Katsumata Yoshinori、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: Oncotarget Volume: 8 Pages: 印刷中
  • DOI: 10.18632/oncotarget.17092
  • Peer Reviewed / Open Access
• [Journal Article] A subtype of idiopathic ventricular fibrillation and its relevance to catheter ablation and genetic variants (2017)
  • Author(s): Nishiyama Takahiko、Aizawa Yoshiyasu、Ito Shogo、Katsumata Yoshinori、Kimura Takehiro、Takatsuki Seiji
  • Journal Title: HeartRhythm Case Rep Volume: 3 Pages: 277～281
  • DOI: 10.1016/j.hrcr.2017.03.004
  • Peer Reviewed / Open Access
• [Journal Article] Tachycardia-Induced J-Wave Changes in Patients With and Without Idiopathic Ventricular Fibrillation (2017)
  • Author(s): Aizawa Yoshiyasu、Takatsuki Seiji、Nishiyama Takahiko、Kimura Takehiro、Kohsaka Shun、Kaneko Yoshiaki、Inden Yasuya、Takahashi Naohiko、Nagase Satoshi、Aizawa Yoshifusa、Fukuda Keichi
  • Journal Title: Circulation: Arrhythmia and Electrophysiology Volume: 10 Pages: e005214～e005214
  • DOI: 10.1161/CIRCEP.117.005214
  • Peer Reviewed
• [Journal Article] Effect of Compliance to Updated AHA/ACC Performance and Quality Measures Among Patients With Atrial Fibrillation on Outcome (from Japanese Multicenter Registry) (2017)
  • Author(s): Inohara Taku、Kimura Takehiro、Ueda Ikuko、Ikemura Nobuhiro、Tanimoto Kojiro、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Nishiyama Takahiko、Katsumata Yoshinori、Fukuda Keiichi、Takatsuki Seiji、Kohsaka Shun
  • Journal Title: The American Journal of Cardiology Volume: 120 Pages: 595～600
  • DOI: 10.1016/j.amjcard.2017.05.029
  • Peer Reviewed
• [Journal Article] Vein of Marshall partially isolated with radiofrequency ablation from the endocardium (2017)
  • Author(s): Kashimura Shin、Nishiyama Takahiko、Kimura Takehiro、Nishiyama Nobuhiro、Aizawa Yoshiyasu、Takatsuki Seiji
  • Journal Title: HeartRhythm Case Rep Volume: 3 Pages: 120～123
  • DOI: 10.1016/j.hrcr.2016.08.008
  • Peer Reviewed / Open Access
• [Journal Article] “J waves” induced after short coupling intervals: a manifestations of latent depolarization abnormality? (2017)
  • Author(s): Aizawa Yoshifusa、Nakayama Masafumi、Sato Masahito、Okabe Masaaki、Aizawa Yoshiyasu、Takatsuki Seiji、Fukuda Keiichi
  • Journal Title: EP Europace Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1093/europace/eux062
  • Peer Reviewed
• [Journal Article] Discrimination between QRS and T Waves Using a Right Parasternal Lead for S-ICD in a Patient with a Single Ventricle (2017)
  • Author(s): NISHIYAMA TAKAHIKO、KIMURA TAKEHIRO、NISHIYAMA NOBUHIRO、AIZAWA YOSHIYASU、FUKUDA KEIICHI、TAKATSUKI SEIJI
  • Journal Title: Pacing and Clinical Electrophysiology Volume: 40 Pages: 904～907
  • DOI: 10.1111/pace.13046
  • Peer Reviewed
• [Journal Article] A Novel SCN5A Mutation Found in a Familial Case of Long QT Syndrome Complicated by Severe Left Ventricular Dysfunction (2017)
  • Author(s): Kimura Mai、Kohno Takashi、Aizawa Yoshiyasu、Inohara Taku、Shiraishi Yasuyuki、Katsumata Yoshinori、Egashira Toru、Fukushima Hiroyuki、Kosaki Kenjiro、Fukuda Keiichi
  • Journal Title: Can J Cardiol Volume: 33 Pages: 554.e5～554.e7
  • DOI: 10.1016/j.cjca.2016.10.010
  • Peer Reviewed
• [Presentation] Unmasking Brugada syndrome behind complete right bundle branch block by ventricular pacing. (2017)
  • Author(s): 52.Yoshiyasu Aizawa, Seiji Takatsuki, Takashi Komatsu, Kazuaki Nakajima, Shogo Ito, Shin Kashimura, Akira Kunitomi, Yoshinori Katsumata, Takahiko Nishiyama, Takehiro Kimura, Nobuhiro Nishiyama, Kotaro Fukumoto, Yoko Tanimoto, Yoshifusa Aizawa, Keiichi Fukuda.
  • Organizer: 第63回日本不整脈心電学会学術大会
  • Int'l Joint Research
• [Presentation] Sex Dependent Risk of Sudden Death or Sick Sinus Syndrome in a Family with Brugada Syndrome. (2017)
  • Author(s): Yoshiyasu Aizawa, Taishi Fujisawa, Yoshinori Katsumata, Seiko Ohno, Keiko Sonoda, Hidemori Hayashi, Rintaro Hojo, Seiji Fukamizu, Takehiro Kimura, Nobuhiro Nishiyama, Yasuo Kurita, Seiji Takatsuki, Satoshi Ogwa, Kenjiro Kosaki, Yuji Nakazato, Minoru Horie, Keiichi Fukuda.
  • Organizer: APHRS2017/JHRS2017
  • Int'l Joint Research
• [Book] EMERGENCY CARE (2018)
  • Author(s): 相澤義泰
  • Total Pages: 9
  • Publisher: メディカ出版