The association between SCN5A, KCNQ1 and KCNE1 gene polymorphisms and complex ventricular arrhythmias in survivors of myocardial infarction.

BACKGROUND Post-MI patients are highly susceptible to sudden cardiac arrest (SCA) and sudden cardiac death (SCD) resulting from ventricular arrhythmia (VA). The search for new clinical predictors to identify those patients who are at the highest risk of these events is therefore essential. Numerous data indicate that the presence of polymorphisms and mutations in the cardiac ion channel genes SCN5A, KCNQ1 and KCNE1 might serve as such a predictor. Since genetic alterations in these genes underlie congenital long QT syndrome (LQTS), which is associated with an increased occurrence of arrhythmic complications and SCD, we decided to verify how alterations in these genes contribute to QT interval abnormalities and consequently to VA, SCA and SCD in post-MI patients. AIM To detect single nucleotide polymorphisms (SNP) in SCN5A, KCNQ1 and KCNE1 of post-MI patients, and to assess whether they are related to electrophysiological markers of cardiac arrhythmia (QT interval) and the clinical course. METHOD The study group consisted of 100 patients (27 females, mean age 69 years) with documented MI 3 months before enrolment. All patients underwent baseline and (after 12 months) control examinations encompassing history, physical examination, basic laboratory analysis, resting 12-lead ECG, 24-hour 12-lead Holter ECG monitoring and echocardiography. Genetic tests were performed during baseline examination. RESULTS In post-MI patients two exonic polymorphisms, H558R in SCN5A and S38G in KCNE1, and two intronic ones, in KCNQ1, were detected. H558R was associated with an increase in QT dispersion (QTd) at minimum and maximum heart rate and QT interval prolongation before premature ventricular beats (PVB), whereas S38G and intronic polymorphisms were related to an increase in QTd before PVB. None of the above polymorphisms was related to complex VA, SCA or SCD. CONCLUSION The above polymorphisms were associated with abnormal repolarisation phase patterns in post-MI patients, which manifested in QT interval prolongation and QTd increase. There was no relationship between these polymorphisms and complex VA, SCA or SCD. The results show that not only exonic alterations but also intronic ones may affect the phenotype.