Holmegard Haya N, Theilade Juliane, Benn Marianne, Duno Morten, Haunso Stig, Svendsen Jesper H
Laboratory of Molecular Cardiology, Copenhagen University Hospital, Copenhagen, Denmark.
Cardiology. 2010;115(3):176-81. doi: 10.1159/000279319. Epub 2010 Jan 29.
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.
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.
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.
Genetic variation in KCNJ3 and KCNJ5 encoding the subunits of the KACh channels is apparently not involved in the pathogenesis of SND.
窦房结功能障碍（SND）是一种病因不明的异质性疾病，其特征为多种室上性心律失常，并伴有晕厥、心悸和头晕症状。异常节律的潜在机制尚未完全明确。
由于迷走神经刺激和乙酰胆碱（ACh）会影响起搏细胞的功能，我们推测编码ACh激活的钾通道（KACh通道）的基因中的遗传变异可能与SND的发病机制有关。
我们筛选了1982年至2005年间在哥本哈根大学医院起搏器登记处登记的、年龄小于60岁且因SND植入起搏器的184例患者。43例患者符合以下纳入标准：记录到窦性停搏、心脏停搏或极度窦性心动过缓。对编码KACh通道主要亚基的KCNJ3和KCNJ5的编码序列进行了重新测序。我们在KCNJ3和KCNJ5中鉴定出了几种已知的单核苷酸多态性，但两个基因均未发现突变。
编码KACh通道亚基的KCNJ3和KCNJ5中的遗传变异显然与SND的发病机制无关。
