Association between HERG K897T polymorphism and QT interval in middle-aged Finnish women

Abstract

Objectives: The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization.

Background: The length of myocardial repolarization, measured as the QT interval, has a hereditary component, but no genes that would explain the variability of repolarization have been identified in healthy subjects.

Methods: QT intervals were measured from the 12-lead electrocardiogram in a random middle-aged population (226 men/187 women). The longest QT interval at any of the 12 leads (QTmax), QTV(2), and the Tpeak-Tend interval were used as measures of repolarization. Deoxyribonucleic acid samples were genotyped for the nucleotide 2690A>C variation of the HERG gene, corresponding to the HERG K(lysine)897T(threonine) amino acid polymorphism.

Results: The allele frequencies were 0.84 (A) and 0.16 (C). Females with the genotype AC or CC had longer QTcmax (477 +/- 99 ms) and Tpeak-Tend intervals (143 +/- 95 ms) than females with the genotype AA (441 +/- 69 ms and 116 +/- 65 ms, p = 0.005 and p = 0.025, respectively). In males, the QTcmax and the Tpeak-Tend intervals did not differ between the genotypes. After adjustment for echocardiographic and various laboratory variables, the HERG K897T polymorphism remained as an independent predictor of QTcmax (p = 0.009) and the Tpeak-Tend intervals (p = 0.026) in females. CONCLUSIONS; The common K897T polymorphism of the HERG channel is associated with the maximal duration and transmural dispersion of ventricular repolarization in middle-aged females.