Pharmacogenetics of cardiac K+ channels

A number of commonly prescribed drugs belonging to various therapeutic clas ses (antiarrhythmic, antibiotic, antifungal, antihistamine, antipsychotic, prokinetic drugs...)possess, in common, the adverse property to prolong car diac repolarization [prolonged QT interval duration on surface electrocardi ogram (ECG)], exposing patients to a risk of torsade-de-pointes arrhythmias , syncope, and sudden death. Arrhythmias related to drug-induced QT prolong ation do not occur in every patient treated with these drugs but most likel y occur in a subset of susceptible patients. These patients have a high ris k of recurrence of arrhythmias upon exposure to any of the other drugs that broaden the QT interval. It is currently suspected (though not yet proven) that susceptible individuals carry a silent mutation in one of the genes r esponsible for the congenital long QT syndrome. Indeed, it appears more and more clear that a large proportion of congenital long QT syndrome gene car riers, have a normal QT interval and a normal phenotype and therefore, rema in undiagnosed. Therefore, a much larger than previously thought proportion of the general population may be affected by asymptomatic mutations in car diac ion channel encoding genes. No routine technology is currently availab le in identifying these patients preventively. (C) 2000 Elsevier Science B. V. All rights reserved.