Abstract
BackgroundMutations 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.MethodsSerial 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.Results96 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.ConclusionMutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a referral clinic population.
Highlights
Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation
Co-expression of the S140G mutant form of KCNQ1 with KCNE1 in COS-7 cells caused increased current density, as well as enhancement of channel activation and inactivation. These observations contrast with the consistent reduction in current density seen with those KCNQ1 mutations associated with LQT1, and with the significant prolongation of the QT interval seen in many of the individuals in the Atrial fibrillation (AF) family
Mutations in KCNQ1 are an uncommon cause of AF in a typical population with the lone form of the arrhythmia[10]
Summary
Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation. Co-expression of the S140G mutant form of KCNQ1 with KCNE1 in COS-7 cells caused increased current density, as well as enhancement of channel activation and inactivation These observations contrast with the consistent reduction in current density seen with those KCNQ1 mutations associated with LQT1, and with the significant prolongation of the QT interval seen in many of the individuals in the AF family. This paradoxical result may reflect unique chamber-specific effects of the mutation or coupling of the channel with different partner proteins, and serves to emphasize that our understanding of repolarization is incomplete. Mutations in KCNQ1 are an uncommon cause of AF in a typical population with the lone form of the arrhythmia[10]
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