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

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

来源：Heart Rhythm, 2012, 9(7): 1099-1103.

DOI：10.1016/j.hrthm.2012.02.019

• Electrocardiogram
• Repolarization
• T wave
• Gene
• Polymorphism

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. %26lt;br%26gt;OBJECTIVE To identify common genetic variants that affect the duration of the TPE interval in the general population. %26lt;br%26gt;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, V-2, and V-5 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. %26lt;br%26gt;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 x 10(-10)). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 x 10(-4)). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 x 10(-14)). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. %26lt;br%26gt;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.

• 出版日期2012-7