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精神分裂症患者抗精神病药引起 QT 间期延长的遗传生物标志物。

Genetic Biomarkers of Antipsychotic-Induced Prolongation of the QT Interval in Patients with Schizophrenia.

机构信息

Institute of Personalized Psychiatry and Neurology, V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia.

Shared Core Facilities "Molecular and Cell Technologies", V. F. Voyno-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia.

出版信息

Int J Mol Sci. 2022 Dec 13;23(24):15786. doi: 10.3390/ijms232415786.

Abstract

Antipsychotics (AP) induced prolongation of the QT interval in patients with schizophrenia (Sch) is an actual interdisciplinary problem as it increases the risk of sudden death syndrome. Long QT syndrome (LQTS) as a cardiac adverse drug reaction is a multifactorial symptomatic disorder, the development of which is influenced by modifying factors (APs' dose, duration of APs therapy, APs polytherapy, and monotherapy, etc.) and non-modifying factors (genetic predisposition, gender, age, etc.). The genetic predisposition to AP-induced LQTS may be due to several causes, including causal mutations in the genes responsible for monoheme forms of LQTS, single nucleotide variants (SNVs) of the candidate genes encoding voltage-dependent ion channels expressed both in the brain and in the heart, and SNVs of candidate genes encoding key enzymes of APs metabolism. This narrative review summarizes the results of genetic studies on AP-induced LQTS and proposes a new personalized approach to assessing the risk of its development (low, moderate, high). We recommend implementation in protocols of primary diagnosis of AP-induced LQTS and medication dispensary additional observations of the risk category of patients receiving APs, deoxyribonucleic acid profiling, regular electrocardiogram monitoring, and regular therapeutic drug monitoring of the blood APs levels.

摘要

抗精神病药(AP)引起的精神分裂症(Sch)患者 QT 间期延长是一个实际的跨学科问题,因为它会增加猝死综合征的风险。长 QT 综合征(LQTS)作为一种药物不良反应是一种多因素的症状性疾病,其发展受到修饰因素(AP 的剂量、AP 治疗持续时间、AP 联合治疗和单药治疗等)和非修饰因素(遗传易感性、性别、年龄等)的影响。AP 引起的 LQTS 的遗传易感性可能是由于几个原因引起的,包括负责单血红素形式 LQTS 的基因中的因果突变、候选基因编码电压依赖性离子通道的单核苷酸变异(SNVs),这些基因在大脑和心脏中均有表达,以及候选基因编码 APs 代谢关键酶的 SNVs。本叙述性综述总结了关于 AP 引起的 LQTS 的遗传研究结果,并提出了一种新的个性化方法来评估其发展的风险(低、中、高)。我们建议在 AP 引起的 LQTS 的初步诊断方案中实施,对接受 AP 治疗的患者进行风险类别的额外观察、脱氧核糖核酸分析、定期心电图监测以及血液中 AP 水平的定期治疗药物监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5671/9785058/84d68a6b1e9c/ijms-23-15786-g001.jpg

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