Koskela Jenni, Kähönen Mika, Fan Meng, Nieminen Tuomo, Lehtinen Rami, Viik Jari, Nikus Kjell, Niemelä Kari, Kööbi Tiit, Turjanmaa Väinö, Pörsti Ilkka, Lehtimäki Terho
Department of Internal Medicine, Tampere University Hospital and Medical School at the University of Tampere, Tampere, Finland.
Transl Res. 2008 Aug;152(2):49-58. doi: 10.1016/j.trsl.2008.06.003. Epub 2008 Jul 23.
T-wave alternans (TWA) in electrocardiography (ECG) is a marker of cardiac repolarization, the molecular regulation of which is incompletely understood. High TWA and prolonged QT intervals are both associated with ventricular arrhythmias and sudden death. Therefore, we tested the hypothesis of whether the same mutations that influence the QT interval also affect TWA variation. We examined the effect of 3 ion channel gene single nucleotide polymorphisms (SNPs), rs1805127, rs727957 KCNE1, and rs1805124 SCN5A, on TWA during a clinical exercise test. A total of 2008 subjects from the Finnish Cardiovascular Study underwent an exercise test with online ECG recording. TWA was measured by using the time-domain, modified moving average method. Maximum values at rest, during maximal exercise, and during recovery were used as outcome measures in statistical analysis. Moreover, 4-year survival data were collected and ion channel SNPs were determined. TWA was lowest in subjects with the TT genotype of rs1805127 during all phases of the exercise test (RANOVA main effect for genotype, P = 0.018). The result remained significant after adjustment for age, existing coronary heart disease, and beta-blocker medication status (RANCOVA, P = 0.035). Of the polymorphisms studied, only rs1805127 had a significant association with mortality (P = 0.047). The most common G-C haplotype, formed by rs727957 and rs1805127, was associated with TWA (RANOVA, P = 0.007) but not with mortality. The rs1805124 polymorphism was not associated with TWA. The common KCNE1 gene variant rs1805127 is associated with TWA during an exercise test in a Finnish population, which provides additional evidence that KCNE1 genetics may influence cardiac repolarization and cardiovascular mortality.
心电图（ECG）中的T波交替（TWA）是心脏复极化的一个标志物，其分子调节机制尚未完全明确。高TWA和延长的QT间期均与室性心律失常和猝死相关。因此，我们检验了影响QT间期的相同突变是否也会影响TWA变化这一假设。我们在一项临床运动试验中研究了3种离子通道基因单核苷酸多态性（SNP），即rs1805127、KCNE1基因的rs727957以及SCN5A基因的rs1805124对TWA的影响。来自芬兰心血管研究的2008名受试者接受了带有在线ECG记录的运动试验。采用时域改良移动平均法测量TWA。静息时、最大运动时和恢复过程中的最大值用作统计分析的结果指标。此外，收集了4年生存数据并确定了离子通道SNP。在运动试验的所有阶段，rs1805127的TT基因型受试者的TWA最低（基因型的重复测量方差分析主效应，P = 0.018）。在调整年龄、现患冠心病和β受体阻滞剂用药状态后，结果仍然显著（协方差分析，P = 0.035）。在所研究的多态性中，只有rs1805127与死亡率有显著关联（P = 0.047）。由rs727957和rs1805127组成的最常见的G-C单倍型与TWA相关（重复测量方差分析，P = 0.007），但与死亡率无关。rs1805124多态性与TWA无关。常见的KCNE1基因变异rs1805127在芬兰人群的运动试验中与TWA相关，这为KCNE1基因可能影响心脏复极化和心血管死亡率提供了额外证据。
