CLINICAL STUDY
association between HERG K897T polymorphism and QT interval in middle-aged finnish women
Eeva Pietilä, BM*,
Heidi Fodstad, MSc ,
Elmo Niskasaari, BM*,
P.äivi J. Laitinen, MSc,
Heikki Swan, MD,
Markku Savolainen, MD*,
Y. Antero Kesäniemi, MD ,
Kimmo Kontula, MD and
Heikki V. Huikuri, MD, FACC*,*
* Division of Cardiology, Department of Medicine, University of Oulu, Oulu, Finland
Department of Medicine, University of Helsinki, Helsinki, Finland
Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Manuscript received December 28, 2001;
revised manuscript received April 8, 2002,
accepted April 30, 2002.
* Reprint requests and correspondence: Dr. Heikki Huikuri, Division of Cardiology, Department of Internal Medicine, University of Oulu. P.O. Box 5000, FIN-90014 University of Oulu, Finland.
heikki.huikuri{at}oulu.fi
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), 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.
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.
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Abbreviations and Acronyms
| | ECG | | electrocardiogram | | Ikr | | rapidly activating delayed rectifier K+ channel | | LQTS | | long QT syndrome | | QTc | | heart rate corrected QT interval | | QTcmax | | heart rate corrected QTmax | | QTcV2 | | heart rate corrected QT interval measured from lead V2 | | TdP | | torsade de pointes |
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