Authors: T. Novotný 1; J. Kadlecová 2; I. Papoušek 3; K. Chroust 3; A. Bittnerová 2; A. Floriánová 1; E. Češková 4; M. Weislamplová 1; V. Pálenský 4; M. Šišáková 1; O. Toman 1; R. Gaillyová 2; J. Špinar 1 Authors‘ workplace: Interní kardiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jindřich Špinar, CSc., FESC 1; Oddělení lékařské genetiky FN Brno, pracoviště Fakultní dětská nemocnice J. G. Mendla, přednosta prim. MUDr. Renata Gaillyová 2; Katedra genetiky a molekulární biologie Přírodovědecké fakulty MU Brno, vedoucí prof. RNDr. Jiří Doškař, CSc. 3; Psychiatrická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Eva Češková, CSc. 4 Published in: Vnitř Lék 2006; 52(2): 116-118 Category: Original Contributions
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.
Group of patients and 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).
Conclusion: Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.
Key words: gene - ion channel - mutation - proarrhythmia - QT interval
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