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Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update

A prolonged QT interval is an important risk factor for ventricular arrhythmias and sudden cardiac death. QT prolongation can be caused by drugs. There are multiple risk factors for drug-induced QT prolongation, including genetic variation. QT prolongation is one of the most common reasons for withd...

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Autores principales: Niemeijer, Maartje N., van den Berg, Marten E., Eijgelsheim, Mark, Rijnbeek, Peter R., Stricker, Bruno H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579250/
https://www.ncbi.nlm.nih.gov/pubmed/26108299
http://dx.doi.org/10.1007/s40264-015-0316-6
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author Niemeijer, Maartje N.
van den Berg, Marten E.
Eijgelsheim, Mark
Rijnbeek, Peter R.
Stricker, Bruno H.
author_facet Niemeijer, Maartje N.
van den Berg, Marten E.
Eijgelsheim, Mark
Rijnbeek, Peter R.
Stricker, Bruno H.
author_sort Niemeijer, Maartje N.
collection PubMed
description A prolonged QT interval is an important risk factor for ventricular arrhythmias and sudden cardiac death. QT prolongation can be caused by drugs. There are multiple risk factors for drug-induced QT prolongation, including genetic variation. QT prolongation is one of the most common reasons for withdrawal of drugs from the market, despite the fact that these drugs may be beneficial for certain patients and not harmful in every patient. Identifying genetic variants associated with drug-induced QT prolongation might add to tailored pharmacotherapy and prevent beneficial drugs from being withdrawn unnecessarily. In this review, our objective was to provide an overview of the genetic background of drug-induced QT prolongation, distinguishing pharmacokinetic and pharmacodynamic pathways. Pharmacokinetic-mediated genetic susceptibility is mainly characterized by variation in genes encoding drug-metabolizing cytochrome P450 enzymes or drug transporters. For instance, the P-glycoprotein drug transporter plays a role in the pharmacokinetic susceptibility of drug-induced QT prolongation. The pharmacodynamic component of genetic susceptibility is mainly characterized by genes known to be associated with QT interval duration in the general population and genes in which the causal mutations of congenital long QT syndromes are located. Ethnicity influences susceptibility to drug-induced QT interval prolongation, with Caucasians being more sensitive than other ethnicities. Research on the association between pharmacogenetic interactions and clinical endpoints such as sudden cardiac death is still limited. Future studies in this area could enable us to determine the risk of arrhythmias more adequately in clinical practice.
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spelling pubmed-45792502015-09-25 Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update Niemeijer, Maartje N. van den Berg, Marten E. Eijgelsheim, Mark Rijnbeek, Peter R. Stricker, Bruno H. Drug Saf Review Article A prolonged QT interval is an important risk factor for ventricular arrhythmias and sudden cardiac death. QT prolongation can be caused by drugs. There are multiple risk factors for drug-induced QT prolongation, including genetic variation. QT prolongation is one of the most common reasons for withdrawal of drugs from the market, despite the fact that these drugs may be beneficial for certain patients and not harmful in every patient. Identifying genetic variants associated with drug-induced QT prolongation might add to tailored pharmacotherapy and prevent beneficial drugs from being withdrawn unnecessarily. In this review, our objective was to provide an overview of the genetic background of drug-induced QT prolongation, distinguishing pharmacokinetic and pharmacodynamic pathways. Pharmacokinetic-mediated genetic susceptibility is mainly characterized by variation in genes encoding drug-metabolizing cytochrome P450 enzymes or drug transporters. For instance, the P-glycoprotein drug transporter plays a role in the pharmacokinetic susceptibility of drug-induced QT prolongation. The pharmacodynamic component of genetic susceptibility is mainly characterized by genes known to be associated with QT interval duration in the general population and genes in which the causal mutations of congenital long QT syndromes are located. Ethnicity influences susceptibility to drug-induced QT interval prolongation, with Caucasians being more sensitive than other ethnicities. Research on the association between pharmacogenetic interactions and clinical endpoints such as sudden cardiac death is still limited. Future studies in this area could enable us to determine the risk of arrhythmias more adequately in clinical practice. Springer International Publishing 2015-06-25 2015 /pmc/articles/PMC4579250/ /pubmed/26108299 http://dx.doi.org/10.1007/s40264-015-0316-6 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review Article
Niemeijer, Maartje N.
van den Berg, Marten E.
Eijgelsheim, Mark
Rijnbeek, Peter R.
Stricker, Bruno H.
Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update
title Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update
title_full Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update
title_fullStr Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update
title_full_unstemmed Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update
title_short Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update
title_sort pharmacogenetics of drug-induced qt interval prolongation: an update
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579250/
https://www.ncbi.nlm.nih.gov/pubmed/26108299
http://dx.doi.org/10.1007/s40264-015-0316-6
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