Molecular Genetic Aspects of Drug-Induced Long QT Syndrome
Long QT syndrome (LQTS) can be both congenital and acquired. The latter one is most often caused by the effects of drugs. Clinical observations show that taking the same doses of drugs has different effects on the duration of the QT interval and the risk of torsades de pointes in different patients. According to the “repolarization reserve” concept, patients with drug-induced LQTS have a genetically programmed low repolarization reserve, i.e. a set of mutations in the genes of ionic transporters that do not manifest clinically prior to the contact with the trigger drug. During the last decade, a number of “latent” mutations in the genes of the congenital LQTS have been identified and functional polymorphisms in the same genes associated with increased susceptibility to the disease have been found. The methods of the whole exome sequencing and genome-wide association studies let to evaluate a wide range of single nucleotide polymorphisms within the entire exome and to investigate the relationship between genomic variants and certain phenotypes. The present review reflects the main advances in the molecular genetic direction of diagnostics of drug-induced LQTS and further prospects for research in this area.