A KCNJ8 mutation associated with early repolarization and atrial fibrillation.

Delaney JT, Muhammad R, Blair MA, Kor K, Fish FA, Roden DM, Darbar D
Europace. 2012 14 (10): 1428-32

PMID: 22562657 · PMCID: PMC3458578 · DOI:10.1093/europace/eus150

AIM - The Kir 6.1 K(atp) channel is believed to play an important role in ventricular repolarization as determined from both functional and genetic studies of the potassium inwardly-rectifying channel, subfamily J, member 8 (KCNJ8)-S422L missense mutation in patients with J-wave syndromes. Although Kir6.1 is also present in atrial tissue, it is unknown whether this channel modulates atrial repolarization and hence whether the S422L mutation portends a greater risk of atrial arrhythmias. This study sought to examine whether there was an increased frequency of the KCNJ8-S422L mutation among patients with atrial fibrillation (AF) and early repolarization (ER) as a possible novel susceptibility gene for AF.

METHODS AND RESULTS - A total of 325 lone AF probands were identified from the Vanderbilt AF Registry, a collection of clinical data and DNA from consented, consecutively enrolled participants. The coding regions of KCNJ8 were sequenced, and the patient's presenting electrocardiogram (ECG) was reviewed by two independent physicians for ER abnormalities. The KCNJ8-S422L mutation was identified in two AF probands while no other candidate gene variants were identified in these cases. Twenty-two (7%) patients were found to have ER on the ECG, including the two probands carrying the S422L variant. In one small AF kindred, the S422L variant co-segregated with AF and ER.

CONCLUSIONS - The KCNJ8-S422L variant is associated with both increased AF susceptibility and ER indicating a role for Kir 6.1 K(atp) channel in both ventricular and atrial repolarization.

MeSH Terms (15)

Adult Atrial Fibrillation Base Sequence Electrocardiography Female Genetic Predisposition to Disease Health Status Indicators Humans KATP Channels Male Middle Aged Molecular Sequence Data Mutation Sequence Analysis, DNA Young Adult

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