Symposium 6

3月26日［金］18:00-19:30

 
  Current perspective on Precision Medicine of Inherited Arrhythmias
  
 
   
  1996年に先天性QT延長症候群(LQTS)患者で初めて原因遺伝子が同定されて以来、多くの不整脈疾患が、心筋イオンチャネルや細胞膜蛋白をコードする遺伝子の変異により発症することが判明した。先天性LQTSでは、75%の患者で原因遺伝子が同定され、遺伝子型(LQT1-3)別の生活指導や治療、すなわち精密医療(Precision Medicine)が実践され、さらに遺伝子変異部位やタイプ別のリスク階層化も行われている。これに対して、ブルガダ症候群では遺伝子診断率が低く(20-30%)、最近では環境因子などの多因子疾患と考えられ、Naチャネル遺伝子であるSCN5Aが唯一病的遺伝子と考えられている。その他の遺伝性不整脈には、カテコラミン誘発多形性心室頻拍(CPVT)、催不整脈性右室心筋症(ARVC)、QT短縮症候群、早期再分極症候群などがある。CPVTも遺伝子診断率の高い疾患で、リアノジン受容体遺伝子をはじめとする幾つかの遺伝子に、ARVCでは、細胞骨格タンパクや接着因子に関連する複数の遺伝子に変異を認め、表現型との関連やリスク階層化についても検討されている。本シンポジウムでは、遺伝性不整脈に焦点をあて、最新の研究成果や知見を発表していただき、不整脈のPrecision Medicineがどこまで進んだかを議論したい。
Since the first causative gene in congenital long QT syndrome (LQTS) was discovered in1996, genetic studies have identified a significant link between mutations in genes encoding for cardiac ion channels or other membrane components and several inherited arrhythmias. The responsible genes mainly KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3) have been identified in 75% of congenital LQTS patients, and genotype-phenotype correlation has been well investigated, enabling genotype-specific management and pharmacological therapy, so-called precision medicine. Moreover, mutation site- or mutation type-specific risk stratification has been introduced in congenital LQTS. Genetic diagnosis rate is less (20-30%) in patients with Brugada syndrome (BrS). Recently, BrS is believed to be multifactorial genetic disorder, and only SCN5A gene is considered to be a pathogenic gene. Other inherited arrhythmias include catecholaminergic polymorphic ventricular tachycardia(CPVT), arrhythmogenic right ventricular cardiomyopathy (ARVC), short QT syndrome, and early repolarization syndrome. Mutations in ryanodine receptor gene (RYR2) are identified in more than 50% of patients with CPVT, and mutations in genes encoding for cytoskeletal and desmosomal proteins have been reported in ARVC patients, in whom genotype-phenotype correlation and risk stratification in relation to causative genes have been evaluated. In this symposium, expert physicians and researchers are welcome to present their own clinical and experimental data and to provide a comprehensive discussion for current perspective on precision medicine of inherited arrhythmias.
 
 
   
 
 
Wataru Shimizua   Wataru Shimizu
Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo
   Arthur Wilde   Arthur Wilde
Heart Centre, Department of Cardiology, Amsterdam UMC, location AMC, Netherlands
 
 
   
 
 
Arthur Wilde   Arthur Wilde
Heart Centre, Department of Cardiology, Amsterdam UMC, location AMC, Netherlands
   Tadashi Nakajima   Tadashi Nakajima
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi
 
 
 
Yukiko Nakano   Yukiko Nakano
Department of Cardiovascular Medicine, Hiroshima University, Hiroshima
   Takeru Makiyama   Takeru Makiyama
Department of Community Medicine Supporting System, Kyoto University Graduate School of Medicine, Kyoto
 
 
 
Hiroshige Murata   Hiroshige Murata
Department of Cardiovascular Medicine, Nippon Medical School, Tokyo