title: Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy.
abstract: BACKGROUND
  Although mutations of several genes are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation between genotype and ventricular arrhythmia features remains unclear. This study was aimed to examine the possible association of the 9 known genes of ARVC with clinical and electrophysiological characteristics.
  
  
  RESULTS
  Ninety subjects diagnosed with ARVC who underwent electrophysiological study were recruited for screening the 9 known ARVC-causing genes. A total of 53 mutations were identified in 57 (63%) subjects. Mutation carriers had more frequent clinical ventricular tachycardia (VT; 89% versus 55%; P<0.001) and negative T waves in V1 to V3 (61% versus 33%; P=0.016). Subjects with plakophilin-2 (PKP2) mutations also had more frequent VT than those without mutations in PKP2. Comparison between subjects with multiple and single mutations showed that syncope occurred more often in the former group (58% versus 24%; P=0.018). VT was significantly more often induced in mutation carriers compared with noncarriers (75% versus 39%; P=0.001), as well as in PKP2 mutation carriers compared with subjects without PKP2 mutations (80% versus 48%; P=0.002). Induced VT with a rate ≥ 200 bpm was more often documented in mutation carriers (88% versus 54%; P=0.013), as well as in PKP2 mutation carriers (91% versus 67%; P=0.041).
  
  
  CONCLUSIONS
  Pathogenic gene mutations were found in nearly two thirds of subjects diagnosed with ARVC. Mutation carriers, especially PKP2, had a higher proportion of a history of VT and more inducible fast VT.
authors.affiliation: Arrhythmia Center and Clinical EP Lab, Sino-German Laboratory for Molecular Medicine, and Hypertension Center, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College-Chinese Academy of Medical Sciences, Beijing, China; and University of Arizona, Tucson, AZ.
authors.forename: Jingru
authors.initials: J
authors.lastname: Bao
authors.forename: Jizheng
authors.initials: J
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yao
authors.forename: Yilu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Fan
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Ding Sheng
authors.initials: DS
authors.lastname: He
authors.forename: Frank I
authors.initials: FI
authors.lastname: Marcus
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
authors.forename: Lei
authors.initials: L
authors.lastname: Song
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000503:physiopathology; D003893:Desmin / Q000235:genetics; D051187:Desmocollins / Q000235:genetics; D051301:Desmoglein 2 / Q000235:genetics; D051180:Desmoplakins / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D051191:Plakophilins / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000235:genetics / Q000503:physiopathology; D053782:Transforming Growth Factor beta3 / Q000235:genetics; D051185:gamma Catenin
chemical_list: C081561:DSC2 protein, human; C495314:DSG2 protein, human; C495294:DSP protein, human; D003893:Desmin; D051187:Desmocollins; D051301:Desmoglein 2; D051180:Desmoplakins; C495292:JUP protein, human; C494847:LMNA protein, human; D034904:Lamin Type A; D008565:Membrane Proteins; C495337:PKP2 protein, human; D051191:Plakophilins; C528696:TMEM43 protein, human; D053782:Transforming Growth Factor beta3; D051185:gamma Catenin
keywords: arrhythmogenic right ventricular dysplasia; genotype; tachycardia, ventricular