The Genetics of Drug-Induced Qt Prolongation: Evaluating the Evidence for Pharmacodynamic Variants

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. 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.

Keywords::

• arrhythmias
• drug-induced QT prolongation
• ionic channels
• pharmacogenetics
• pharmacogenomics
• polymorphism
• torsades de pointes
• variant

Financial & competing interests disclosure

JA Luzum is supported by the National Heart, Lung, and Blood Institute of the NIH (K08 HL146990 and L30 HL110279). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

JA Luzum is supported by the National Heart, Lung, and Blood Institute of the NIH (K08 HL146990 and L30 HL110279). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.