Genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants: supplemental material

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. KCNE1-D85N and KCNE2-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.

药物诱导性长QT综合征（drug-induced long QT syndrome, diLQTS）是多种临床常用处方药的不良反应，可增加致死性室性心律失常的发病风险。已有研究显示药效学基因的遗传变异与diLQTS存在关联，但目前尚未针对上述各类变异的证据强度开展评估。因此，本综述旨在采用一种基于先天性长QT综合征（congenital LQTS）研究方法改良的新型半定量评分系统，对与diLQTS相关的药效学遗传变异的证据强度进行评估。其中KCNE1-D85N与KCNE2-T8A分别对应diLQTS的确定性证据与强证据等级。上述变异所具备的高证据等级，支持其可作为接受QT延长药物治疗患者的风险因素这一当前临床观点。