Genetic variation in the inwardly rectifying K channel subunits KCNJ3 (GIRK1) and KCNJ5 (GIRK4) in patients with sinus node dysfunction

TY - JOUR

T1 - Genetic variation in the inwardly rectifying K channel subunits KCNJ3 (GIRK1) and KCNJ5 (GIRK4) in patients with sinus node dysfunction

AU - Holmegard, Haya N

AU - Theilade, Juliane

AU - Benn, Marianne

AU - Duno, Morten

AU - Haunso, Stig

AU - Svendsen, Jesper H

AU - Holmegard, Haya N

AU - Theilade, Juliane

AU - Benn, Marianne

AU - Dunø, Morten

AU - Haunso, Stig

AU - Svendsen, Jesper H

N1 - Keywords: Adolescent; Adult; Aged; Alleles; Amino Acid Substitution; DNA Mutational Analysis; Female; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Genotype; Humans; Male; Middle Aged; Pacemaker, Artificial; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Reference Values; Sequence Analysis, DNA; Sick Sinus Syndrome; Young Adult

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

U2 - 10.1159/000279319

DO - 10.1159/000279319

M3 - Journal article

C2 - 20110696

SN - 0008-6312

VL - 115

SP - 176

EP - 181

JO - Cardiology

JF - Cardiology

IS - 3

ER -