P5857Study of pharmacodynamic and pharmacokinetic-mediated genetic susceptibility to drug-induced arrhythmia and sudden cardiac death

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Introduction: Drug-induced arrhythmia is a rare clinical event that can be potentially fatal. It is mostly related to polymorphic ventricular tachycardia Torsade de Pointes and drug-induced QT (diQT) prolongation, one of the most common causes of drug withdrawal from the market. To the date, several risk factors have been described to be related to these fatal events, including preexistent cardiac disease and genetic variation. Purpose: The objective of this project was to study the genetic factors that predispose to drug-induced arrhythmias and sudden cardiac death (SCD). Methods: The study was performed by analysing target genes associated with pharmacodynamic and pharmacokinetic pathways of psychotropic drugs in 31 polymedicated patients suspected of having drug-induced channelopathy or SCD. In the pharmacodynamic study, 96 genes associated with SCD were analysed by massive parallel sequencing. Detected variants were prioritized according to their possible pathogenicity by functional impact on the protein, allele frequency in population databases, in silico pathogenicity prediction, conservation and published literature.

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