Genetic Variation in the Inwardly Rectifying K~+ Channel Subunits KCNJ3 (GIRK1) and KCNJ5 (GIRK4) in Patients with Sinus Node Dysfunction

摘要

Background: Sinus node dysfunction (SND) is a heterogeneous disorder of unknown etiology characterized by a variety of supraventricular arrhythmias with symptoms of syncope, palpitations, and dizziness. The mechanism underlying the abnormal rhythm is incompletely understood. Objective: Because vagal stimulation and acetylcholine (ACh) affect the function of pacemaker cells, we hypothesized that genetic variation in the genes encoding the ACh-activated K~+ channels, the KACh channels, could be involved in the pathogenesis of SND. Methods and Results: We screened 184 patients listed in the pacemaker registry of the Copenhagen University Hospital aged <60 years at pacemaker implantation for SND in the period 1982-2005. Forty-three patients fulfilled the following inclusion criteria: documented sinus arrest, asystole, or extreme sinus bradycardia. The coding sequences of KCNJ3 and KCNJ5, encoding the main subunits of the KACh channels, were re-sequenced. We identified several known single nucleotide polymorphisms in KCNJ3 and KCNJ5, but no mutations in either of the genes. Conclusions: Genetic variation in KCNJ3 and KCNJ5 encoding the subunits of the KACh channels is apparently not involved in the pathogenesis of SND.