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药物引起的 QT 间期延长的遗传学:评估药效动力学变异的证据。

The genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants.

机构信息

Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.

Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Pharmacogenomics. 2022 Jun;23(9):543-557. doi: 10.2217/pgs-2022-0027. Epub 2022 Jun 14.

Abstract

Drug-induced long QT syndrome (diLQTS) is an adverse effect of many commonly prescribed drugs, and it can increase the risk for lethal ventricular arrhythmias. Genetic variants in pharmacodynamic genes have been associated with diLQTS, but the strength of the evidence for each of those variants has not yet been evaluated. Therefore, the purpose of this review was to evaluate the strength of the evidence for pharmacodynamic genetic variants associated with diLQTS using a novel, semiquantitative scoring system modified from the approach used for congenital LQTS. D85N and -T8A had definitive and strong evidence for diLQTS, respectively. The high level of evidence for these variants supports current consideration as risk factors for patients that will be prescribed a QT-prolonging drug.

摘要

药物引起的长 QT 综合征(diLQTS)是许多常用药物的不良反应,可增加致命性室性心律失常的风险。药效基因的遗传变异与 diLQTS 相关,但尚未评估每种变异的证据强度。因此,本综述的目的是使用改良自先天性长 QT 综合征的方法的新型半定量评分系统评估与 diLQTS 相关的药效遗传变异的证据强度。D85N 和 -T8A 分别与 diLQTS 具有明确和强有力的证据。这些变异的高证据水平支持目前将其视为将开处 QT 延长药物的患者的危险因素的考虑。

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