title: Mutation analysis ion channel genes ventricular fibrillation survivors with coronary artery disease.
abstract: BACKGROUND
  Observations from population-based studies demonstrated a strong genetic component of sudden cardiac death. The aim of this study was to test the hypothesis that ion channel genes mutations are more common in ventricular fibrillation (VF) survivors with coronary artery disease (CAD) compared to controls.
  
  
  METHODS
  The entire coding sequence of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was analyzed in 45 (five females) CAD individuals-survivors of documented VF and in 90 matched healthy controls. In another control group of 141 matched patients with CAD without malignant arrhythmias, the exons containing rare coding variants found in the VF survivors were sequenced.
  
  
  RESULTS
  The carrier frequency of all the rare sequence variants was significantly higher in the VF survivors (8/45, 17.8%) than in CAD controls (3/141, 2.2%, P = 0.001). In VF survivors, four coding variants in eight individuals were found. Three in KCNH2 gene: R148W and GAG186del are novel; P347S was previously related to long QT syndrome. In SCN5A gene, P2006A variant was found in five unrelated males. This variant has been demonstrated previously to have small effect on sodium channel kinetics. No rare coding variants were found in the healthy controls. The P2006A variant was found in three CAD controls.
  
  
  CONCLUSIONS
  The prevalence of selected, rare coding variants in five long QT genes was significantly higher in cases versus controls, confirming a mechanistic role for these genes among a subgroup of patients with coronary disease and VF.
authors.affiliation: Department of Internal Medicine and Cardiology, University Hospital Brno and Faculty of Medicine of Masaryk University, Brno, Czech Republic. novotny-t@seznam.cz
authors.forename: Tomas
authors.initials: T
authors.lastname: Novotny
authors.forename: Jitka
authors.initials: J
authors.lastname: Kadlecova
authors.forename: Martina
authors.initials: M
authors.lastname: Raudenska
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bittnerova
authors.forename: Irena
authors.initials: I
authors.lastname: Andrsova
authors.forename: Alena
authors.initials: A
authors.lastname: Florianova
authors.forename: Anna
authors.initials: A
authors.lastname: Vasku
authors.forename: Petr
authors.initials: P
authors.lastname: Neugebauer
authors.forename: Milan
authors.initials: M
authors.lastname: Kozak
authors.forename: Milan
authors.initials: M
authors.lastname: Sepsi
authors.forename: Lubomir
authors.initials: L
authors.lastname: Krivan
authors.forename: Renata
authors.initials: R
authors.lastname: Gaillyova
authors.forename: Jindrich
authors.initials: J
authors.lastname: Spinar
mesh_terms: D000368:Aged; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality*; D018153:Czech Republic / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D017741:Survivors; D014693:Ventricular Fibrillation / Q000235:genetics* / Q000401:mortality*
chemical_list: D015221:Potassium Channels