Koskela J, Laiho J, KäHönen M, Rontu R, Lehtinen R, Viik J, Niemi M, Niemelä K, Kööbi T, Turjanmaa V, Pörsti I, Lehtimäki T, Nieminen T
Internal Medicine, Tampere University Hospital and Tampere University Medical School, Tampere, Finland.
Scand J Clin Lab Invest. 2008;68(1):31-8. doi: 10.1080/00365510701496488.
Cardiac repolarization is regulated, in part, by the KCNH2 gene, which encodes a rapidly activating component of the delayed rectifier potassium channel. The gene expresses a functional single nucleotide polymorphism, K897T, which changes the biophysical properties of the channel. The objective of this study was to evaluate whether this polymorphism influences two indices of repolarization--the QT interval and T-wave alternans (TWA)--during different phases of a physical exercise test.
The cohort consisted of 1,975 patients undergoing an exercise test during which on-line electrocardiographic data were registered. Information on coronary risk factors and medication was recorded. The 2690A>C nucleotide variation in the KCNH2 gene corresponding to the K897T amino acid change was analysed after polymerase chain reaction with allele-specific TaqMan probes.
Among all subjects, the QTc intervals did not differ between the three genotype groups (p> or =0.31, RANOVA). Women with the CC genotype tended to have longer QT intervals during the exercise test, but the difference was statistically significant only at rest (p = 0.011, ANOVA). This difference was also detected when the analysis was adjusted for several factors influencing the QT interval. No statistically significant effects of the K897T polymorphism on TWA were observed among all subjects (p = 0.16, RANOVA), nor in men and women separately.
The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the TWA, but the influence of the CC genotype on QT interval deserves further research among women.
心脏复极部分受KCNH2基因调控，该基因编码延迟整流钾通道的快速激活成分。该基因存在一种功能性单核苷酸多态性，即K897T，它会改变通道的生物物理特性。本研究的目的是评估这种多态性在体育锻炼测试的不同阶段是否会影响两个复极指标——QT间期和T波交替（TWA）。
该队列由1975名接受运动测试的患者组成，测试过程中记录在线心电图数据。记录冠状动脉危险因素和用药信息。使用等位基因特异性TaqMan探针进行聚合酶链反应后，分析KCNH2基因中对应K897T氨基酸变化的2690A>C核苷酸变异。
在所有受试者中，三个基因型组之间的QTc间期无差异（p≥0.31，重复测量方差分析）。CC基因型的女性在运动测试期间QT间期往往较长，但差异仅在静息时具有统计学意义（p = 0.011，方差分析）。在对影响QT间期的多个因素进行校正后，也检测到了这种差异。在所有受试者中，未观察到K897T多态性对TWA有统计学意义的影响（p = 0.16，重复测量方差分析），男性和女性单独分析时也未观察到。
KCNH2基因的K897T多态性可能不是TWA的主要遗传决定因素，但CC基因型对QT间期的影响值得在女性中进一步研究。
