Yamaguchi Yoshiaki, Mizumaki Koichi, Hata Yukiko, Sakamoto Tamotsu, Nakatani Yosuke, Kataoka Naoya, Ichida Fukiko, Inoue Hiroshi, Nishida Naoki
Second Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Clinical Research and Ethics Center, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Heart Vessels. 2017 Feb;32(2):186-192. doi: 10.1007/s00380-016-0859-1. Epub 2016 Jun 2.
KCNE1 encodes a modulator of KCNQ1 and KCNH2 channels. Although KCNE1(G38S), a single-nucleotide polymorphism (SNP) causing a G38S substitution in KCNE1, is found frequently, whether and how this SNP causes long QT syndrome (LQTS) remains unclear. We evaluated rate-dependent repolarization dynamics using Holter electrocardiogram (ECG) to assess the pathogenicity of KCNE1(G38S). Forty-five patients exhibiting long QT intervals, as assessed by their baseline ECGs, and 16 control subjects were enrolled. KCNE1(G38S) carriers were identified using genome sequencing. LQTS patients were classified into LQT1 or LQT2 using genetic analysis or epinephrine test. QT-RR relations were determined using 24-h Holter ECG recordings. Among the 15 patients (33.3 %) with KCNE1(G38S), four patients without any mutations or amino acid changes in other major cardiac ion channels were categorized as KCNE1(G38S) carriers. In the QT-RR regression lines, the QT-RR slope was greater in the KCNE1(G38S) carriers and the LQT2 patients (0.215 ± 0.021 and 0.207 ± 0.032, respectively) than in the LQT1 patients (0.163 ± 0.014, P < 0.05) and the control subjects (0.135 ± 0.025, P < 0.001). The calculated QT intervals at an RR interval of 1200 ms were longer in the KCNE1(G38S) carriers and LQT1 and LQT2 patients than in the control subjects. Patients with KCNE1(G38S) had a rate-dependent repolarization abnormality similar to patients with LQT2 and, therefore, may have a potential risk to develop lethal arrhythmias.
KCNE1编码KCNQ1和KCNH2通道的一种调节剂。尽管经常发现KCNE1（G38S）这种导致KCNE1中G38S替换的单核苷酸多态性（SNP），但该SNP是否以及如何导致长QT综合征（LQTS）仍不清楚。我们使用动态心电图（ECG）评估心率依赖性复极动力学，以评估KCNE1（G38S）的致病性。纳入了45例经基线心电图评估显示QT间期延长的患者和16名对照受试者。使用基因组测序鉴定KCNE1（G38S）携带者。通过基因分析或肾上腺素试验将LQTS患者分为LQT1或LQT2。使用24小时动态心电图记录确定QT-RR关系。在15例（33.3%）携带KCNE1（G38S）的患者中，4例在其他主要心脏离子通道中没有任何突变或氨基酸变化的患者被归类为KCNE1（G38S）携带者。在QT-RR回归线中，KCNE1（G38S）携带者和LQT2患者（分别为0.215±0.021和0.207±0.032）的QT-RR斜率大于LQT1患者（0.163±0.014，P<0.05）和对照受试者（0.135±0.025，P<0.001）。在RR间期为1200毫秒时，KCNE1（G38S）携带者以及LQT1和LQT2患者计算出的QT间期长于对照受试者。携带KCNE1（G38S）的患者具有与LQT2患者相似的心率依赖性复极异常，因此可能有发生致命性心律失常的潜在风险。
