Relationship of the expression of calcium-handling proteins in the sarcoplasmic reticulum with polymorphic variants of their genes and with structural and functional parameters of the heart in patients with atrial fibrillation

Abstract

Aim. To investigate the relationship between the expression of Ca2+ handling proteins of the sarcoplasmic reticulum, polymorphic variants of their genes, and structural and functional parameters of the heart in patients with atrial fibrillation (AF).Materials and methods. The study included patients with AF. The patients underwent radiofrequency ablation, during which a myocardial biopsy was taken. The patients underwent echocardiography (EchoCG) before surgery. Polymorphic variants rs1860561 of the ATP2A2 gene and rs6684209 and rs7521023 of the CASQ2 gene were determined in the patients by real-time polymerase chain reaction (PCR), and the level of expression of SERCA2a and CASQ2 proteins in the myocardium was detected by immunoblotting.Results. Carriers of the GG genotype at rs1860561 of the ATP2A2 gene and CC genotype at rs6684209 of the CASQ2 gene were characterized by significantly higher expression of the corresponding proteins. Using cluster analysis, we identified groups of patients by the level of SERCA2a and CASQ2 expression: group 1 – patients with low protein content; group 2 – patients with high protein content. According to clinical and anamnestic parameters, the patients in the selected groups were homogeneous. In patients with high SERCA2a levels, the end systolic and diastolic volumes of the left ventricle (LV) were significantly higher than those in patients with low levels of this protein. The rates of early (peak E) and late left ventricular diastolic filling (peak A) were significantly lower in the group with high SERCA2a expression. A comparative analysis of EchoCG data of patients distributed by the level of CASQ2 expression in the myocardium did not reveal significant differences between the groups.Conclusion. The polymorphic variant rs1860561 of the ATP2A2 gene and rs6684209 of the CASQ2 gene can modulate the level of SERCA2a and CASQ2 expression. SERCA2a expression is associated with the functional and structural parameters of the heart in patients with AF.

Keywords

• фибрилляция предсердий
• са2+-атфаза саркоплазматического ретикулума
• кальсеквестрин
• полиморфные варианты генов
• эхокардиография