Molecular Diagnosis & Therapy

, Volume 10, Issue 3, pp 153-162

First online:

Pharmacogenetic Issues in Thorough QT Trials

  • Richard S. JudsonAffiliated withSpyroPharma
  • , Benjamin A. SalisburyAffiliated withClinical Data, Inc. Email author 
  • , Carol R. ReedAffiliated withClinical Data, Inc.
  • , Michael J. AckermanAffiliated withSudden Death Genomics Laboratory, Mayo Clinic College of Medicine

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market.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.