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


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.
Holmegard
Haya N
HN
Laboratory of Molecular Cardiology, Copenhagen University Hospital, Copenhagen, Denmark.
Theilade
Juliane
J
Benn
Marianne
M
Duno
Morten
M
Haunso
Stig
S
Svendsen
Jesper H
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012016:Reference Values; D017422:Sequence Analysis, DNA; D012804:Sick Sinus Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D055815:Young Adult
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497066:KCNJ3 protein, human; C484274:KCNJ5 protein, human