Impact of mineralocorticoid receptor gene NRC2 on the prediction of arrhythmia after acute myocardial infarction

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with acute myocardial infarction (AMI) suffer from distress that causes a rise in cortisol (stress hormone) which acts through glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). Both receptors are present in cardiomyocyte nuclei (1-4). The animal model study in 2017 showed that activated MR increases cardiomyocyte oxidative stress leading to adverse electrophysiological remodelling that causes arrhythmias. 1.4% of tachyarrhythmias which is the main cause of cardiac death occur within the first month in AMI patients. MR are encoded by the human gene NR3C2 (nuclear receptor subfamily 3 group C member (5-6). Thus, we hypothesized that NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms might have an extensive impact on rhythm disorders that occur in a cohort of AMI patients. Aim The aim is to evaluate the impact of the NR3C2 rs2070950, rs4635799 and rs5522 genes polymorphism in patients that developed rhythm and conduction disorders after suffering AMI. Methods The study included 301 patients treated at our hospital after suffering from AMI; all study subjects underwent primary percutaneous coronary intervention (PCI) and guideline-directed medical treatment (1). Patients' blood samples that were collected upon arrival had cortisol and troponin I levels checked and SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) assessed. To avoid inaccuracies all patients with a previous history of coronary syndrome or PCI were excluded. Rhythm conduction disorders and NR3C2 gene polymorphism were analyzed using the exact Fisher’s test. All the statistical analyses were performed with SPSS 27.0 software. The value of p < 0.05 was considered statistically significant. Results Patients with ventricular and atrial events in the early phase of AMI had higher levels of serum cortisol than the patients that did not have rhythm disorders (p=0.001) (Table 1). Rhythm disorders such as ventricular tachycardia (VT), ventricular flutter (VF) and atrial flutter or atrial fibrillation (AF/AFL) that occurred during hospitalization for AMI were notably associated with rs5522 gene polymorphism. During a hospital stay for AMI higher rs5522 TT genotype frequency was noticed in patients with AF/AFL than in patients without. C allele recurrence was 19.6%. Moreover, the protective effect was detected for AF/AFL there is also a protective effect in VA. (Table 2). Despite this, the gene polymorphism and high-grade atrioventricular block (HAVB) were unrelated. Genes rs2070950 and rs4635799 were not found significant to rhythm and conduction disorders. Conclusions Patients with the rs5522 TT allele are more prone to experience a higher frequency of arrhythmias. However, if at least one rs5522 C is found it associates with a smaller risk of arrhythmias post-AMI, meaning that this gene possibly limits damaging effects on cardiomyocytes that are caused by cortisol.