Left ventricular myocardial remodeling in hypertensive men with heart failure: focus on SNP rs7069102 SIRT1 gene phenotypes

Abstract

Myocardial remodeling in essential hypertension (EH) is an integral stage in the formation of heart failure (HF) on its background, and it may be under genetic control. The study of phenotypic manifestations of SNP rs7069102 of the sirtuin 1 (SIRT1) gene is a promising direction of research into the genetics of EH, because the expression product of this SNP is involved in the formation of age-related changes in the heart, the regulation of the processes of energy supply, hypertrophy and fibrosis of the myocardium.The aim of the study was to evaluate the role of SNP rs7069102 of the SIRT1 gene in the processes of myocardial remodeling in men with chronic heart failure (CHF), which complicated the EH, residents of the Podilsk region of Ukraine. Material and methods. 190 men aged 40-65, residents of the Podilsk region of Ukraine, were examined: 70 people without cardiovascular diseases formed a control group, the main group included 60 patients with asymptomatic EH and 60 patients with CHF II A stage. The molecular genetic study of SNP rs7069102 of the SIRT1 gene was carried out by the method of allele-specific polymerase chain reaction (PCR). All study participants underwent Doppler echocardiography according to a standard protocol. Statistical analysis was performed using contingency table analysis, analysis of variance, and odds ratio calculation. Results. It was found that, in general, among men, residents of the Podilsk region of Ukraine, carriers of the G allele dominate (70.26%), while among patients with EH, GG homozygotes are significantly more common (53.34%) than among men of the control group (35, 31%, p<0.001). It was determined that for GG homozygotes the risk of developing EH is significantly higher than for carriers of other SNP variants (the model is reliable at χ2=4.31, p=0.042, OR= 2.06). GG homozygotes are also characterized by certain features of hypertensive remodeling of the myocardium in the form of significantly greater wall thickness (1.23±0.02 cm, p<0.05) and larger left ventricular size (LV=74.04±1.27 ml/m2, p<0.05) and the left atrium size (iLA=38.56±0.56 ml/m2, p<0.05), higher LV myocardial mass index (iMMLV=87.58±2.24 g/m2, 7, p<0.05), lower indicators of diastolic function (E/A=0.85±0.05 human units, p<0.05) and systolic function (LVEF ejection fraction=41.68±0.77 %, p<0.05), than in carriers of the СG+GG variant. In conclusion, the carrier of the homozygous GG variant for patients with EH, including, in case of development of CHF, is associated with a higher probability of having LV and LA dilatation, LV diastolic dysfunction, and a CHF phenotype with a decrease LVEF below 40%.Conclusions. Thus, SNP rs7069102 of the SIRT1 gene is associated not only with a higher risk of developing EH, but also with such variants of heart remodeling that may underlie the formation of CHF on its background.