A common variant near the KCNJ2 gene is associated with T-peak to T-end interval

Annukka Marjamaa, Lasse Oikarinen, Kimmo Porthan, Samuli Ripatti, Gina Peloso, Peter A. Noseworthy, Matti Viitasalo, Markku S. Nieminen, Lauri Toivonen, Kimmo Kontula, Leena Peltonen, Aki S. Havulinna, Antti Jula, Christopher J. O'Donnell, Christopher Newton-Cheh, Markus Perola, Veikko Salomaa

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

BACKGROUND: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE: To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS: We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V2, and V5 on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS: We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10-10). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10-4). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10-14). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION: The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.

Original languageEnglish (US)
Pages (from-to)1099-1103
Number of pages5
JournalHeart rhythm
Volume9
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • Electrocardiogram
  • Gene
  • Polymorphism
  • Repolarization
  • T wave

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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