Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy.
Neuropsychobiology. 2019;77(2):67-72. doi: 10.1159/000493400. Epub 2018 Dec 13.
Several antipsychotics and antidepressants have been associated with electrocardiogram alterations, the most clinically relevant of which is the heart rate-corrected QT interval (QTc) prolongation, a risk factor for sudden cardiac death. Genetic variants influence drug-induced QTc prolongation and can provide valuable information for precision medicine. The effect of genetic variants on QTc prolongation as well as the possible interaction between polymorphisms and risk medications in determining QTc prolongation were investigated. Medications were classified according to their known risk of inducing QTc prolongation (high-to-moderate, low, and no risk). QTc duration and risk of QTc > median value were investigated in a sample of 77 patients with mood or psychotic disorders being treated with antidepressants and antipsychotics, and who had at least 1 ECG recording. A secondary analysis considered QTc percentage change in patients (n = 25) with 2 ECG recordings. Single-nucleotide polymorphisms previously associated with QTc prolongation during treatment with psychotropic medications were investigated. No association survived after multiple-testing correction. The best results for modulation of QTc duration were identified for rs10808071 (the ABCB1 gene, nominal p = 0.007) when at least 1 medication with a moderate-to-high risk was prescribed, and for rs12029454 (the NOS1AP gene) in patients taking at least 1 medication with a cardiovascular risk (nominal p = 0.008). In the secondary analysis, rs2072413 (the KCNH2 gene) was the top finding for the modulation of QTc percentage change (nominal p = 0.001) when 1 drug with a moderate-to-high risk was added compared to baseline. Despite the limited power of this study, our results suggest that ABCB1, NOS1AP, and KCNH2 may play a role in QTc duration/prolongation during treatment with psychotropic drugs.
几种抗精神病药和抗抑郁药已被证明与心电图改变有关，其中最具临床意义的是心率校正 QT 间期（QTc）延长，这是心源性猝死的一个危险因素。遗传变异影响药物引起的 QTc 延长，并可为精准医学提供有价值的信息。本研究旨在调查遗传变异对 QTc 延长的影响，以及多态性与决定 QTc 延长的风险药物之间的可能相互作用。根据已知引起 QTc 延长的风险（高-中度、低和无风险）对药物进行分类。在 77 名接受抗抑郁药和抗精神病药治疗的心境或精神病障碍患者的样本中，我们调查了 QTc 持续时间和 QTc 值超过中位数的风险，这些患者至少有 1 份心电图记录。在 2 份心电图记录的患者（n = 25）中进行了二次分析，考虑了 QTc 百分比变化。研究了先前与精神药物治疗期间 QTc 延长相关的单核苷酸多态性。经多次测试校正后，没有一个结果有统计学意义。当至少有一种中度至高度风险的药物处方时，rs10808071（ABCB1 基因，名义 p = 0.007）对 QTc 持续时间的调节效果最佳，当患者服用至少一种有心血管风险的药物时，rs12029454（NOS1AP 基因）的调节效果最佳（名义 p = 0.008）。在二次分析中，与基线相比，当添加 1 种中度至高度风险药物时，rs2072413（KCNH2 基因）对 QTc 百分比变化的调节作用是最佳发现（名义 p = 0.001）。尽管本研究的效力有限，但我们的结果表明，ABCB1、NOS1AP 和 KCNH2 可能在精神药物治疗期间的 QTc 持续时间/延长中起作用。
