Aim: The BNP biomarker application optimization for myocardial dysfunction diagnosis in men citizens of Podillia region in Ukraine with uncomplicated essential hypertension and left ventricular hypertrophy by determining the plasma levels in patients with different BNP gene variants. Methods. We examined 141 men, age 40-60 years, who live in Podillia region. Among them 62 men were diagnosed uncomplicated EH with left ventricular hypertrophy (stages 1 and 2) and CHF I-II classes according to NYHA Classification. 79 healthy men were included into the control group. The patients with uncomplicated EH and the healthy men were representative by age. The BNP (T-381C) gene polymorphism was determined by PCR, and the level of BNP plasma concentrations was established by ELISA. Results. In both healthy men and patients with uncomplicated EH with LVH, residents of Podillia region, age 40-60 years, dominates the T381C genotype and the C allele of the BNP gene. It was found that any inherited variant of the BNP gene was not associated with the risk of developing uncomplicated EH with LVH in men residents of Podillia region. However, carriers of the C381C genotype and the C allele of the BNP gene have significantly higher levels of BNP in plasma in both healthy men and patients with uncomplicated EH and LVH, residents of Podillia region, age 40-60 years. There are calculated levels of BNP that can be used for screening of large groups of people for early diagnosis of uncomplicated EH with LVH: BNP boundary level ≥ 82,41 pg/ml ables to diagnose uncomplicated EH with LVH in male carriers of the C allele heterozygote carriers of the genotypes T381C and C381C of the BNP gene; BNP boundary level ≥ 45,34 pg/ml ables to diagnose uncomplicated EH with LVH in male homozygote carriers of the T381T genotype of the BNP gene.

Aim:To improve diagnosis of the severity of essential hypertension in men citizens of Podillia region in Ukraine by determining the plasma levels of ET-1 in patients with different ET-1 gene variants. Methods. We examined 141 men aged 40 -60 years old, who live in Podillia region in Ukraine. Among them 62 men were diagnosed uncomplicated EH with left ventricular hypertrophy and CHF I classe according to NYHA Classification. 79 healthy men were included into a control group. The patients with uncomplicated EH and the healthy men were representative by age. The ET-1 (Lys198Asn) gene polymorphism was determined by PCR, and the level of ET-1 plasma concentrations was established by ELISA. Results. In both healthy men and patients with uncomplicated EH with LVH, residents of Podillia region in Ukraine aged 40-60 years old, dominates Lys198Lys genotype and Lys allele of the ET-1 gene. It was found that any inherited variant of the ET-1 gene was not associated with the risk of developing uncomplicated EH with LVH in men residents of Podillia region in Ukraine. However, the carriers of the Asn allele of the ET-1 gene have significantly higher levels of ET-1 in plasma in both healthy men and patients with uncomplicated EH and LVH. There are calculated levels of ET-1 that can be used for screening of large groups of people for early diagnosis of uncomplicated EH with LVH in carriers of the Asn allele and carriers of the genotype Lys198Lys of the ET-1 gene.

Despite overall effort hypertensive disease (HD) is one of the most significant health and social problem. Essential hypertension is believed to be a multifactorial disease and polymorphism of genes that may be responsible for the regulation of blood pressure plays the key role in it. The least explored in this regard is single nucleotide polymorphism of ET-1 leading to the replacement of the amino acids of lysine (Lys) to asparagine (Asn) at position of 198th polypeptide chain (Lys198Asn).The objective of the research was to improve diagnosis of HD severity determining plasma concentration of ET-1, C-type natriuretic peptides (CNP) and the coefficient of CNP/ET-1 in patients with different genotypes of ET-1 gene.Materials and methods. The study involved 79 men without cardiovascular diseases (control group), 62 men with II stage HD and 50 men with HD complicated by chronic heart failure (CHF) II-III classes according to NYHA Classification. All patients were representative by age. Genotyping of ET-1 gene was conducted using polymerase chain reaction. ET-1 concentration in plasma was determined using ELISA method.Results. Lys/Lys genotype of ET-1 gene was found to occur in 65.82% of men in the control group, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) constituted 34.18%, Lys allele was observed in 79.75% of cases, Asn allele was detected in 20.25% of men. Among patients with II stage HD Lys/Lys genotype of ET-1 gene was observed in 56.45% of cases, the carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) occurred in 43.55% of patients, Lys allele was found in 73.39% of cases, Asn allele was observed in 26.61% of patients. Among men with HD and CHF IIA genotype Lys/Lys was found in 66.00% of cases, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) was observed in 34.00% of patients, Lys allele was detected in 80.00% of cases, Asn allele was observed in 20.00% of cases. The men from the control group, patients with II stage HD and patients with HD and CHF as the carriers of Asn allele were found to have significantly higher plasma levels of ET-1 (2.53±0.12 fmol/ml, 13.90±0.22 fmol/ml and 14.07±0.18 fmol/ml, respectively) and CNP (2.98±0.08 pmol/ml, 5.90±0.11 pmol/ml and 5.93±0.18 pmol/ml, respectively) in comparison with homozygous carriers of Lys genotype (ET-1constituted 1.41±0.05 fmol/ml, 11.58±0.23 fmol/ml and 0.08±12.89 fmol/ml, respectively, CNP constituted 2.02±0.29 pmol/ml, 4.68±0.12 pmol/ml and 4.88±0.09 pmol/ml, respectively). According to the analysis of the obtained data, coefficient of CNP/ET-1 (0.40±0.003 c.u. and 0.38±0.006 c.u., respectively) and Asn allele (0.42±0.004 c.u. and 0.42±0.007 c.u., respectively) was significantly lower in patients with II stage HD and patients with HD and CHF as the carriers of Lys/Lys genotype in comparison with the control group (1.4±0.04 c.u. and 1.22±0.05 c.u., respectively). Carriers of Asn allele in the control group had significantly lower coefficient of CNP/ET-1 than genotype Lys/Lys carriers. However, the difference in the coefficient of CNP/ET-1 was not observed in patients with HD.Conclusions. Lys/Lys genotype and Lys allele of ET-1 gene were found to dominate among control group and patients with HD of different severity. Plasma concentration of ET-1, CNP were significantly higher and coefficient of CNP/ET-1 was lower in men with II stage HD and HD complicated by CHF than in men without cardiovascular diseases in case of all ET-1 gene genotypes. The carriers of Asn allele of ET-1 gene had significantly higher plasma levels of ET-1 and CNP in each study group.

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Annotation. According to multiple studies hypertension (AH) is a multifactorial disease. It is recognized that one of the key mechanisms of persistent increase in blood pressure (BP) is the imbalance between vasoconstriction and vasodilation and endothelial dysfunction (ED) is one of the leading links in the pathogenesis of AH. The consequence of ED is a persistent vasoconstrictor reaction which results in myocardial remodeling in the form of left ventricular hypertrophy (LVH) and the subsequent development of congestive heart failure (CHF). One of the most important representatives of the group of vasoconstrictor peptides is endothelin-1 (ET-1). It has been previously shown that the polymorphism of the gene encoding it (Lys198Asn) is associated with fluctuations in ET-1 plasma concentration. In this regard, the corresponding changes in plasma levels of one of the most powerful vasodilators – C-natriuretic peptide (CNP) – remain poorly understood. CNP is a direct antagonist of ET-1 which increases in the blood in AH and can be used as a screening method to identify patients with high BP. The aim of the study – improving the detection of men with AH who has persistent long-term elevations in BP by using the plasma level of CNP and taking into account the carrier of polymorphic variants of the ET-1 gene. The study involved 191 men aged 40-60 years: 79 men were from control group, 62 patients with AH and LVH and 50 patients with AH complicated by CHF II-III classes for NYHA. Enzyme-linked immunosorbent assay was used to determine the plasma concentration of CNP. Genotyping of the ET-1 gene was performed using the polymerase chain reaction. Mathematical processing was performed on a personal computer using the standard statistical package STATISTICA 6.0. It is established that plasma CNP levels in men with AH and LVH (5.21±0.11) pmol/ml and in patients with AH and CHF (5.22±0.13) pmol/ml are significantly higher than in control patients (2.35±0.06) pmol/ml (p<0.0001) however did not differ in patients with AH from different groups. The obtained results allowed to calculate the limit level of CNP which is ≥3.37 pmol/ml and can be used for screening detection of males with persistently elevated BP in the survey of large populations. It was found that in patients with AH as in the control group the Lys/Lys genotype and the Lys allele of the ET-1 gene predominate. There was no significant difference in the frequency of ET-1 gene between groups (p>0.05). It should be noted that in patients with AH carrying all polymorphic variants of the ET-1 gene the level of CNP in blood was also significantly higher than in the control group, however in carriers of the Asn allele plasma level of CNP is higher than in individuals with the Lys/Lys genotype in all study groups. So it was investigated that the average plasma concentration of CNP in patients with AH is higher than in the control group which made it possible to establish a limit level of peptide for screening of individuals with persistent long-term elevation of BP. In men of the control group and in patients with AH the carrier of the Asn allele of the ET-1 gene is associated with a higher level of CNP but in all study groups the Lys/Lys genotype and the Lys allele of the ET-1 gene were dominant.