Paavonen Kristian J, Swan Heikki, Piippo Kirsi, Laitinen Päivi, Fodstad Heidi, Sarna Seppo, Toivonen Lauri, Kontula Kimmo, Viitasalo Matti
Department of Medicine, University of Helsinki, 00290 Helsinki, Finland.
Int J Cardiol. 2007 May 31;118(2):197-202. doi: 10.1016/j.ijcard.2006.06.050. Epub 2006 Oct 4.
The most prevalent LQT1 form of inherited long QT syndrome is caused by mutations of the KCNQ1 gene resulting repolarizing I(Ks) potassium current to decrease and the QT interval to prolong. As abrupt sympathetic activation triggers ventricular arrhythmias that may cause syncopal attacks and sudden death in LQT1 patients, we investigated whether two known beta1-adrenergic receptor polymorphisms were associated with the duration of QT interval or history of symptoms in LQT1.
We determined beta1-adrenergic receptor polymorphisms (Ser49Gly and Arg389Gly) in 168 LQT1 patients. We also reviewed each patient's clinical records on the history of long QT syndrome-related symptoms and measured QT intervals from baseline ECG in each subject and from an exercise test ECG in 55 LQT1 patients.
Patients with the homozygous Arg389Arg genotype tended to have shorter and those with the Ser49Ser genotype longer QT intervals than patients with other genotypes, but neither polymorphism studied alone affected the risk of symptoms. In contrast, adjusted odds ratio for the history of symptoms was 4.9 (95% CI 1.18 to 20.3) in patients homozygous for both Ser49 and Arg389. These double homozygous patients showed similar QT intervals as the rest of the LQT1 cohort.
In this relatively small study, double homozygosity for Arg389 and Ser49 of the human beta1-adrenergic receptor associated with the risk of symptoms in LQT1. The association between these beta1-adrenergic receptor polymorphisms and the symptom history in LQT1 is not mediated via QT interval duration.
遗传性长QT综合征最常见的LQT1型是由KCNQ1基因突变引起的，导致复极化I(Ks)钾电流降低，QT间期延长。由于突然的交感神经激活会触发室性心律失常，可能导致LQT1患者晕厥发作和猝死，我们研究了两种已知的β1-肾上腺素能受体多态性是否与LQT1患者的QT间期持续时间或症状史有关。
我们测定了168例LQT1患者的β1-肾上腺素能受体多态性（Ser49Gly和Arg389Gly）。我们还查阅了每位患者与长QT综合征相关症状史的临床记录，并测量了每位受试者基线心电图以及55例LQT1患者运动试验心电图的QT间期。
与其他基因型患者相比，纯合子Arg389Arg基因型患者的QT间期往往较短，而Ser49Ser基因型患者的QT间期较长，但单独研究的这两种多态性均未影响症状风险。相比之下，Ser49和Arg389均为纯合子的患者出现症状史的调整优势比为4.9（95%可信区间为1.18至20.3）。这些双重纯合子患者的QT间期与LQT1队列中的其他患者相似。
在这项相对较小的研究中，人类β1-肾上腺素能受体的Arg389和Ser49双重纯合性与LQT1患者的症状风险相关。这些β1-肾上腺素能受体多态性与LQT1患者症状史之间的关联不是通过QT间期持续时间介导的。
