title: [Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation].
abstract: BACKGROUND
  In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions.
  
  
  METHODS
  Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome).
  
  
  RESULTS
  At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature).
  
  
  CONCLUSIONS
  Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.
authors.affiliation: Interní kardiologická klinika Lékarské fakulty MU a FN Brno. novotny-t@seznam.cz
authors.forename: T
authors.initials: T
authors.lastname: Novotný
authors.forename: J
authors.initials: J
authors.lastname: Kadlecová
authors.forename: I
authors.initials: I
authors.lastname: Papousek
authors.forename: K
authors.initials: K
authors.lastname: Chroust
authors.forename: A
authors.initials: A
authors.lastname: Bittnerová
authors.forename: A
authors.initials: A
authors.lastname: Floriánová
authors.forename: E
authors.initials: E
authors.lastname: Cesková
authors.forename: M
authors.initials: M
authors.lastname: Weislamplová
authors.forename: V
authors.initials: V
authors.lastname: Pálenský
authors.forename: M
authors.initials: M
authors.lastname: Sisáková
authors.forename: O
authors.initials: O
authors.lastname: Toman
authors.forename: R
authors.initials: R
authors.lastname: Gaillyová
authors.forename: J
authors.initials: J
authors.lastname: Spinar
mesh_terms: D004252:DNA Mutational Analysis; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D015221:Potassium Channels / Q000235:genetics*
chemical_list: D015221:Potassium Channels