Contribution of genetic variability of the proinflammatory cytokine system to the development of long QT syndrome

Objective. To evaluate the contribution of genetic variability in the proinflammatory cytokine system to the development of druginduced long QT syndrome (LQTS). Materials and methods. 129 patients with cardiac arrhythmias taking Class III antiarrhythmic drugs (amiodarone or sotalol) were examined. Depending on the presence or absence of drug-induced LQTS, patients were divided into 2 groups: group 1 (n = 64) – with QT interval prolongation; group 2 (n = 65) – without QT interval prolongation. Forty individuals without a history of cardiac arrhythmias served as a control group. All patients underwent polymerase chain reaction analysis for the T31C and C3953T polymorphisms in the IL-1b gene, C3872T in the CRP gene, G308A in the TNF-α gene, and G174C in the IL-6 gene. Statistical analysis was performed using Statistica 12.0. Results. The most pronounced effect was demonstrated by the combination of the CT genotype of the IL-1b gene C3953T polymorphism, the GC genotype of the IL-6 gene G174C polymorphism, and the GA genotype of the TNF-α gene G308A polymorphism. These genotypes increased the risk of developing LQTS by 5.26 times (95 % CI (1.42–19.50), p = 0.013). Using the Fruchterman – Reingold algorithm, the G308A polymorphism of the TNF-α gene (9.16 %), the C3953T polymorphism of the IL-1b gene (8.95 %), and the G174C polymorphism of the IL-6 gene (6.31 %) had the greatest predictive potential for the development of LQTS. The greatest genegene interaction effect was demonstrated by combinations of the G308A TNF-α gene and C3872 CRP gene polymorphisms (5.22 %), as well as the G308A TNF-α gene and T31C IL-1b gene polymorphisms (3.49 %). Conclusion. The obtained data support the possible involvement of the proinflammatory cytokine genetic polymorphism system in the regulation of drug-induced LQTS development. A putative mechanism for this association may be the varying degrees of activation of potassium and calcium ion channels in response to the causative drug, which depends, among other things, on the patient's blood cytokine concentration.