association between HERG K897T polymorphism and QT interval in middle-aged finnish women

• Published in: Journal of the American College of Cardiology Vol. 40; no. 3; pp. 511 - 514
• Main Authors: Pietilä, Eeva, Fodstad, Heidi, Niskasaari, Elmo, Laitinen, P.äivi J, Swan, Heikki, Savolainen, Markku, Kesäniemi, Y.Antero, Kontula, Kimmo, Huikuri, Heikki V
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 07.08.2002; Elsevier Science; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Body Mass Index; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiology; Cardiology. Vascular system; Cation Transport Proteins; Confidence intervals; Deoxyribonucleic acid; DNA; DNA-Binding Proteins; Electric properties; Electrocardiography; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Female; Finland - epidemiology; Gender; Gene Frequency - genetics; Genotype; Heart; Heart rate; Heart Rate - genetics; Humans; Long QT syndrome; Male; Medical sciences; Middle age; Middle Aged; Multivariate Analysis; Polymorphism, Genetic - genetics; Population; Potassium Channels - genetics; Potassium Channels, Voltage-Gated; Predictive Value of Tests; Reference Values; Studies; Trans-Activators; Transcriptional Regulator ERG; Women; Women's Health; Europe; Finland; Ikr; QTc; QTcV2; TdP; QTcmax; LQTS; ECG; Human; QT interval; Wave burst; Arrhythmia; Pathogenesis; Potassium ion; Sex; Cardiovascular disease; Ionic channel; Genetic determinism; Excitability disorder; Electrodiagnosis; Gene; Heart disease; Electrocardiography; Female; Polymorphism
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(02)01979-4

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. 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. 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), QTV2, 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. 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. The common K897T polymorphism of the HERG channel is associated with the maximal duration and transmural dispersion of ventricular repolarization in middle-aged females.