title: Torsades de pointes complicating atrioventricular block: evidence for a genetic predisposition.
abstract: BACKGROUND
  The prevalence of genetic risk factors has not been systematically evaluated in the setting of complete atriventricular (AV) block complicated by long QT syndrome (LQTS).
  
  
  OBJECTIVE
  This study was performed to determine to what extent acquired LQTS in the context of AV block has a genetic substrate.
  
  
  METHODS
  Among 420 recipients of pacemakers implanted over a 3-year period, we identified retrospectively 29 patients with complete AV block and a QT interval >600 ms in duration. A second study group included 22 randomly selected patients who had AV block and a QT interval <600 ms. Normal controls were 100 consecutive individuals without medical history. Genetic studies screening for HERG, KCNQ1 KCNE1, KCNE2, and SCN5A mutations were performed.
  
  
  RESULTS
  We identified four mutations on genes encoding potassium channels in five patients with AV block and acquired LQTS. These mutations were not found among patients with AV block and a QT interval <600 ms in duration or in healthy volunteers. Functional expression of three HERG mutations (R328C, R696C, and R1047L) had a dominant negative effect on wild-type I(Kr). One KCNE2 mutation (R77W) identified in a patient treated with flecainide did not alter I(Kr).
  
  
  CONCLUSIONS
  This study showed that complete AV block complicated by LQTS was associated with HERG mutations in 17% of cases. Further studies are needed to identify factors, genetic or environmental, which may be implicated in bradycardia-related abnormalities of ventricular repolarization.
authors.affiliation: Hôpital Cardiologique, Hospices Civils de Lyon, Lyon, France. philippe.chevalier@chu-lyon.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Chevalier
authors.forename: Chloé
authors.initials: C
authors.lastname: Bellocq
authors.forename: Gilles
authors.initials: G
authors.lastname: Millat
authors.forename: Eric
authors.initials: E
authors.lastname: Piqueras
authors.forename: Franck
authors.initials: F
authors.lastname: Potet
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Schott
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baró
authors.forename: Hervé
authors.initials: H
authors.lastname: Lemarec
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Robert
authors.initials: R
authors.lastname: Rousson
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006327:Heart Block / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D012189:Retrospective Studies; D016171:Torsades de Pointes / Q000209:etiology / Q000235:genetics*
chemical_list: D015221:Potassium Channels