Relationship of the Polymorphic Variant Rs989692 of the Neprilysin Gene (Mme) With the Levels of Natriuretic Peptides and Its Clinical Significance in Patients With Heart Failure and Atrial Fibrillation

Background. The variability in the activity of natriuretic peptides (NUPs) is determined genetically, as evidenced by the association of polymorphic variants encoding brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) with an increased risk of cardiovascular (CV) disease. The aim of the study. To determine the frequency of alleles and genotypes of the SNP rs989692 of the neprilysin gene (MME). To determine the association of SNP rs989692 in MME with the concentration of NUP and soluble neprilysin and to evaluate its prognostic value in relation to the development of adverse cardiovascular events in patients with heart failure (HF) associated with a left ventricular ejection fraction (LVEF) <50% and persistent or long-term persistent atrial fibrillation (AF). Material and methods. The main group included 152 patients with HF, the control group included 35 individuals without CV disease. The levels of ANP, BNP, NT-proBNP and soluble neprilysin were determined for all patients. The genetic study of the SNP rs989692 in the MME gene was carried out by polymerase chain reaction. The endpoint: hospitalization due to HF progression. The composite endpoint: hospitalization due to HF progression, new onset or progressive exertional angina pectoris, myocardial infarction. Results. The frequency distribution of genotypes and alleles of the SNP rs989692 in MME did not differ significantly between the control and experimental groups. The levels of ANP, BNP and neprilysin in patients with HF in combination with AF did not differ depending on the SNP rs989692 in MME genotype. Patients with HF associated with LVEF <50%, AF and TT genotype rs989692 in MME had higher levels of NT-proBNP (those with CC genotype – 964 [655.1; 1724] pg/ml, those with TC genotype – 1074.1 [857; 1944] pg/ml, those with the TT genotype – 2992 [886; 4885] pg/ml, p<0.05). The presence of the homozygous TT genotype in patients with HF combined with LVEF <50% and AF was associated with an increased risk of developing adverse CV events, OR=1.9 [95% CI from 1.2 to 3.09]. Conclusion. Patients with HF associated with LVEF <50% in combination with permanent or long-term persistent AF with homozygous TT genotype rs989692 of the MME gene have higher levels of NT-proBNP and a higher risk of developing adverse cardiovascular events.