Akyol Mahmut, Jalilzadeh Shapour, Sinner Moritz F, Perz Siegfried, Beckmann Britt M, Gieger Christian, Illig Thomas, Wichmann H-Erich, Meitinger Thomas, Kääb Stefan, Pfeufer Arne
Institute of Human Genetics, GSF National Research Centre of Environment and Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany.
Eur Heart J. 2007 Feb;28(3):305-9. doi: 10.1093/eurheartj/ehl460. Epub 2007 Jan 16.
The QT interval in the general population is a complex trait with 30-50% heritability. QT prolongation is associated with an increased risk of sudden death. A recent family-based study found an association between QT interval and the common non-synonymous Glycin 38 Serine variant (G38S, rs1805127) of the KCNE1 gene coding for the minK-potassium channel subunit. We intended to replicate this finding in a large population sample of central European Caucasian ancestry as part of our ongoing search for genetic variants predisposing to arrhythmias.
We studied 3966 unrelated individuals from the KORA S4 population-based study without atrial fibrillation, pacemaker implant, or pregnancy. Individuals were genotyped by MALDI-TOF mass spectrometry. We did not detect any significant association between the genotypes of the G38S variant and the QT interval in the entire population or in any gender.
Unlike the common Lysine 897 Threonine variant of KCNH2 (K897T, rs1805123) the G38S variant of KCNE1 does not appear to have a strong modifying effect on QT interval. However, we cannot rule out an effect of G38S on QT in other ethnic groups, under exercise or medications or on the risk for arrhythmias and sudden death.
普通人群的QT间期是一种具有30%-50%遗传度的复杂性状。QT间期延长与猝死风险增加相关。最近一项基于家系的研究发现,QT间期与编码minK钾通道亚基的KCNE1基因常见的非同义甘氨酸38丝氨酸变异(G38S,rs1805127)之间存在关联。作为我们正在进行的心律失常易感基因变异研究的一部分,我们打算在大量中欧高加索血统的人群样本中重复这一发现。
我们研究了来自基于人群的KORA S4研究的3966名无房颤、未植入起搏器且未怀孕的无关个体。通过基质辅助激光解吸电离飞行时间质谱法对个体进行基因分型。在整个人群或任何性别中,我们均未检测到G38S变异的基因型与QT间期之间存在任何显著关联。
与KCNH2常见的赖氨酸897苏氨酸变异(K897T,rs1805123)不同,KCNE1的G38S变异似乎对QT间期没有强烈的修饰作用。然而,我们不能排除G38S在其他种族群体中、运动或用药情况下对QT的影响,以及对心律失常和猝死风险的影响。