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

    Ana I Lopez-Medina

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

    ,
    Choudhary Anwar A Chahal

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

    Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA

    Barts Heart Centre, St. Bartholomew’s Hospital, West Smithfield, London, EC1A 7BE, UK

    WellSpan Health, Lancaster, PA 17607, USA

    &
    Jasmine A Luzum

    *Author for correspondence: Tel.: +1 734 615 4851;

    E-mail Address: jluzum@med.umich.edu

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

    Published Online:https://doi.org/10.2217/pgs-2022-0027

    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.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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