Judson Richard S, Salisbury Benjamin A, Reed Carol R, Ackerman Michael J
SpyroPharma, Guilford, Connecticut, USA.
Mol Diagn Ther. 2006;10(3):153-62. doi: 10.1007/BF03256454.
Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market. As a consequence, the US FDA and other regulatory agencies are mandating that all new drugs go through a so-called 'Thorough QT' (TQT) study to evaluate the potential for 'QT liability', specifically the potential for a drug to cause a discernible increase in the QT interval. Several genetic factors that modulate the risk of DI-LQT have been discovered. These are genes responsible for the congenital long QT syndrome, drug metabolism genes (mainly CYP2D6 and CYP3A4), and genes in other regulatory pathways. Here, we briefly review the links between genetic variants and drug-induced QT risk, and propose approaches to consider for using pharmacogenetics in planning and analyzing TQT studies.
药物诱导的QT间期延长（DI-LQT）及其相关心律失常是药物退市的主要原因。因此，美国食品药品监督管理局（FDA）和其他监管机构要求所有新药都要进行所谓的“全面QT”（TQT）研究，以评估“QT风险”，特别是药物导致QT间期明显延长的可能性。已经发现了几种调节DI-LQT风险的遗传因素。这些基因包括导致先天性长QT综合征的基因、药物代谢基因（主要是CYP2D6和CYP3A4）以及其他调节途径中的基因。在此，我们简要回顾遗传变异与药物诱导的QT风险之间的联系，并提出在规划和分析TQT研究时考虑使用药物遗传学的方法。
