title: A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction.
abstract: BACKGROUND
  Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).
  
  
  METHODS
  We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).
  
  
  RESULTS
  Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).
  
  
  CONCLUSIONS
  One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Reza
authors.initials: R
authors.lastname: Jabbari
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Glinge
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Javad
authors.initials: J
authors.lastname: Jabbari
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bjarke
authors.initials: B
authors.lastname: Risgaard
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bo Gregers
authors.initials: BG
authors.lastname: Winkel
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Christian Juhl
authors.initials: CJ
authors.lastname: Terkelsen
authors.affiliation: Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Tilsted
authors.affiliation: Department of Cardiology, Odense University Hospital, Odense, Denmark.
authors.forename: Lisette Okkels
authors.initials: LO
authors.lastname: Jensen
authors.affiliation: Department of Cardiology, Odense University Hospital, Odense, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Hougaard
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.|Laboratory of Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Engstrøm
authors.affiliation: Center for Arrhythmia Prevention, Division of Preventive Medicine, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Albert
authors.affiliation: Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Tfelt-Hansen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014693:Ventricular Fibrillation / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human