title: Potassium channel gene mutations rarely cause atrial fibrillation.
abstract: BACKGROUND
  Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation. In order to explore the role of potassium channels in inherited typical forms of the arrhythmia, we have screened a cohort of patients from a referral clinic for mutations in the channel subunit genes implicated in the arrhythmia. We sought to determine if mutations in KCNJ2 and KCNE1-5 are a common cause of atrial fibrillation.
  
  
  METHODS
  Serial patients with lone atrial fibrillation or atrial fibrillation with hypertension were enrolled between June 1, 2001 and January 6, 2005. Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiogram and blood sample for genetic analysis were also obtained. Patients with a family history of AF were screened for mutations in KCNJ2 and KCNE1-5 using automated sequencing.
  
  
  RESULTS
  96 patients with familial atrial fibrillation were enrolled. Eighty-three patients had lone atrial fibrillation and 13 had atrial fibrillation and hypertension. Patients had a mean age of 56 years at enrollment and 46 years at onset of atrial fibrillation. Eighty-one percent of patients had paroxysmal atrial fibrillation at enrollment. Unlike patients with an activating mutation in KCNQ1, the patients had a normal QTc interval with a mean of 412 +/- 42 ms. Echocardiography revealed a normal mean ejection fraction of 62.0 +/- 7.2 % and mean left atrial dimension of 39.9 +/- 7.0 mm. A number of common polymorphisms in KCNJ2 and KCNE1-5 were identified, but no mutations were detected.
  
  
  CONCLUSIONS
  Mutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a referral clinic population.
authors.affiliation: Cardiovascular Research Center and Cardiac Arrhythmia Service Massachusetts General Hospital, Boston, Massachusetts, USA. pellinor@partners.org
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Vadim I
authors.initials: VI
authors.lastname: Petrov-Kondratov
authors.forename: Elena
authors.initials: E
authors.lastname: Zakharova
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Nam
authors.forename: Calum A
authors.initials: CA
authors.lastname: MacRae
mesh_terms: D001281:Atrial Fibrillation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics
chemical_list: C489457:KCNJ2 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated