title: Latent pathogenicity of the G38S polymorphism of KCNE1 K+channel modulator.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Clinical Research and Ethics Center, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. kmizu@med.u-toyama.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizumaki
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hata
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kataoka
authors.affiliation: Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Fukiko
authors.initials: F
authors.lastname: Ichida
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishida
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D015716:Electrocardiography, Ambulatory; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D016014:Linear Models; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D055815:Young Adult
chemical_list: C489622:KCNE1 protein, human; D024642:Potassium Channels, Voltage-Gated
keywords: Arrhythmia; KCNE1; Long QT syndrome; QT–RR relation