Abstract
Several studies have associated mutations in genes encoding potassium channels and accessory subunits involved in cardiac repolarization with increased susceptibility of atrial fibrillation (AF). Recently, the Krüppel-like factor 15 (Klf15) was found to transcriptionally control rhythmic expression of KChIP2, a critical subunit required for generating the transient outward potassium current (Ito), and that deficiency or excess of Klf15 increased the susceptibility of arrhythmias. On this basis we hypothesized that mutations in Klf15 could be associated with AF. A total of 209 unrelated Caucasian lone AF patients were screened for mutations in Klf15 by direct sequencing. No mutations in the lone AF cohort were found. In one patient we found a synonymous variant (c.36C > T). In NHLBI GO Exome Sequencing Project (ESP) the variant was present in 31 of 4269 Caucasian individuals and in 3 of 2200 African Americans. In our cohort Klf15 was not associated with lone AF.
Highlights
Several studies have associated mutations in genes encoding potassium channels and accessory subunits involved in cardiac repolarization with susceptibility of atrial fibrillation (AF)
On this basis we hypothesized that mutations in Krüppel-like factor 15 (Klf15), because of its regulatory role of Ito, could be associated with susceptibility of AF
We found no mutations in Klf15 in our AF cohort
Summary
Several studies have associated mutations in genes encoding potassium channels and accessory subunits involved in cardiac repolarization with susceptibility of atrial fibrillation (AF). In a recent Nature paper by Jeyaraj et al (2012) the Krüppel-like factor 15 (Klf15) was found to transcriptionally control rhythmic expression of KChIP2, a critical subunit required for generating Ito (Kuo et al, 2001), and that deficiency or excess of Klf increased susceptibility of ventricular arrhythmias. All these data definitely suggest that disturbances in cardiac potassium current, whether it is through mutations in α-subunits, β-subunits, or regulatory subunits, play a significant role in the pathogenesis of AF. On this basis we hypothesized that mutations in Klf, because of its regulatory role of Ito, could be associated with susceptibility of AF
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