Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study

Abstract

Objective. 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. Material and methods. 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. Results. Among all subjects, the QTc intervals did not differ between the three genotype groups (p⩾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. Conclusions. 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.

• Arrhythmia
• beta‐adrenergic blockers
• electrocardiography
• ion channels
• polymorphism

Acknowledgements

We thank Ms. Marita Koli and Nina Peltonen for their skilful technical assistance, and the staff in the Department of Clinical Physiology for collecting the exercise test data. Grants: the Emil Aaltonen Foundation, the Finnish Foundation of Cardiovascular Research, the Pirkanmaa Regional Fund of the Finnish Cultural Foundation, the Tuberculosis Foundation of Tampere and Competitive research funding of the Pirkanmaa Hospital District. J.K. and J.L. contributed equally to this work.