[Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation].
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.
Novotný
T
T
Interní kardiologická klinika Lékarské fakulty MU a FN Brno. novotny-t@seznam.cz
Kadlecová
J
J
Papousek
I
I
Chroust
K
K
Bittnerová
A
A
Floriánová
A
A
Cesková
E
E
Weislamplová
M
M
Pálenský
V
V
Sisáková
M
M
Toman
O
O
Gaillyová
R
R
Spinar
J
J
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*
D015221:Potassium Channels