Objective: To evaluate the role of the polymorphism of AGT genes (rs4762) and GNB3 genes (rs5443) in the development of the essential arterial hypertension separately and by combining their polymorphic variants. Design and method: The case-control study involved 100 patients with EAH stage II, 1-3 degrees of blood pressure (BP), high and very high cardiovascular risk. Among the patients there were 21% (21) men, 79% (79) women. The mean age of patients was 59.86±6.22y.o. The control group consisted of 60 almost healthy individuals, relevant in age (49.13±6.28y.o.) and gender distribution (63% - women, 37% - men). To study of polymorphism of AGT (rs4762) and GNB3 (rs5443) genes was performed a qualitative polymerase chain reaction (PCR) in real time. Results: The mutated T-allele of the AGT gene (rs4762) occurs in 15.97% of hypertensive residents of Northern Bukovyna, that is more frequent than in healthy individuals by 9.72% (p = 0.023); homozygous mutations of the AGT gene were not found in the control group at all. Whereas, the relative frequency of polymorphic variants of the GNB3 gene (rs5443, 825C>T) did not differ significantly between groups. The wild C-allele statistically significantly prevails over the mutated T-allele in both groups according to the AGT (rs4762) and GNB3 (rs5443) genes (p<0.001). Binary logistic regression confirmed an increase in the risk of hypertension inheritance according to dominant and additive models in minor T-allele carriers of the AGT gene (rs4762) almost 3 times higher than in C-allele homozygotes (p = 0.04 and p = 0.03). Inheritance of EAH is not associated with polymorphic variants of the GNB3 gene (rs5443). Conclusions: The T-allele of the AGT gene (rs4762) increases the risk of hypertension almost 3 times, whereas, polymorphic variants of the GNB3 gene (rs5443) are not predictors of EAH in the observed.

Objective: Endothelial dysfunction (ED) is an initial step to vascular insufficiency, atherosclerosis. The study is aimed to clarify the risk of ED and carotid arteries (CA) intima media thickness (IMT) changes depending on guanine-nucleotide-binding-protein-beta-3 (GNB3, rs5443) and endothelial-nitric-oxide-synthase (NOS3, rs2070744) genes’ polymorphisms in essential arterial hypertension (EAH). Design and method: One-hundred EAH patients with target-organ damage, moderate/high/very high cardiovascular risk were involved in the case-control study: 79.0% females, 21.0% males, mean age 59.87±8.02; disease duration 6-25 years. Control - 48 practically healthy persons . GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphisms examined in Real-Time-PCR. Soluble-Vascular-Cell-Adhesion-Molecule (sVCAM-1), total NO-metabolites (NO2-/NO3-), transcriptional activity of NOS3 gene, Endothelium-Dependent-Flow-Mediated-Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied. Results: Severe EAH course (SBP/DBP>160>100 mmHg) is associated with the structural changes of the CA (IMT>0.9 mm) increasing the likelihood more than 3.5 times [OR 95%CI:1.28-10.23; p = 0.012], atherosclerotic plaques on the CA – 4 and 3.5 times as much [OR 95%CI:1.18-13.59; p = 0.018 and 1.23-10.71; p = 0.014], and decreased NOS3 gene transcriptional activity by the mRNA level (<0.5 U) – threefold [OR 95%CI: 1.0-9.66; p = 0.042]). Moderate/severe ED enhance the risk of severe EAH 3-5.5 times [OR 95%CI:1.13-9.34; p = 0.025 and 1.96-14.45; p<0.001]. C-allele of NOS3 (rs2070744) gene elevates the risk of atherosclerotic lesion in CA 3.5 times [OR 95%CI:1.24-11.20; p = 0.019 and 1.22-10.18; p = 0.018], ED – by decrease of total NO metabolites (<25 μmol/l) and sVCAM-1 growth (>1050 ng/ml) almost 12 and 4 times [OR 95%CI: 1.23-112.7; p = 0.023 and 1.24-11.20; p = 0.019]. C-allele of NOS3 gene heighten the probability of low NOS3 gene expression by mRNA level (<0.5 U) 69 times [OR95%CI:17,72-520,0; p<0,001]. Minor T-allele (rs5443) increases the risk of CA changes by IMT (>0,9 mm) threefold [OR 95%CI:1.09-7.74; p = 0.027], CA atherosclerotic plaques – almost 10 and 5 times [OR 95%CI:2.55-38.0; p<0.001 and 1.61-13.27; p = 0.003]. T-allele of GNB3 gene enhances the probability of high sVCAM-1 (>1050 ng/ml) threefold [OR 95%CI:1.06-9.59; p = 0.032]. Conclusions: C-allele of NOS3 (rs2070744) gene contributes more to ED risk elevation. T-allele of GNB3 (rs5443) gene increases the risk of the carotid arteries structural changes.

Objective: The aim of this study was to establish the role of clinical complains and symptoms as risk factors for severe essential arterial hypertension (EAH) in patients with vitamin D deficiency. Design and method: 100 EAH patients with target-organ damage, moderate, high-very high cardiovascular risk were involved in the case-control study. 79.0% females and 21.0% males, mean age 59.87 ± 8.02. They were tested for total serum 25-hydroxyvitamin D concentration (immune luminescent test “MAGLUMI”, “SNIB”, China). All recruited patients were taken history, underwent complex examination and divided into groups depending on level of vitamin D and BP. Control group included 60 practically healthy persons of relevant age. Results: Hypertensive patients with vitamin D deficiency complained on heart pain 14.23% (⇙2 = 2.17; p>0.05), arrythmias – 20.86% (2 = 3.86; p = 0.049), headache – by 27.89% (⇙2 = 7.34; p = 0.007), sleep disturbance – by 29.77% (⇙2 = 7.97; p = 0.005), weakness and fatigue – by 20,59% (⇙2 = 3.88; p = 0.049) more frequent, than patients with normal 25-hydroxyvitamin D concentration. The frequency of patients with fatal cardiovascular risk SCORE >5.0 with vitamin D deficiency prevailed the ones with a normal level of vitamin D – by 20.94% (⇙2 = 3.98; p = 0.046). The risk for arrhythmias, weakness and fatigue increases 1.5 times [OR–2.36; 95% CI OR:1.0–5.61; p0.049 and OR–2.40; 95% CI OR:1.0-5.79; p = 0.049], sleep disturbance, headache and overweight increases 1.7-2.35 times [OR–3.43; 95% CI OR: 1.43-8.22; p = 0.005 and [OR–3.63; 95% CI OR:1.39-9.49; p = 0.007] and [OR–11.50; 95%CI OR:1.33-99.33; p = 0.038], respectively) in patients with 2nd-3d degree of BP elevation and vitamin D deficiency. The fatal cardiovascular risk SCORE >5.0 increases 1.5 times [OR–2.34; 95% CI OR:1.01-5.45; p = 0.046] in hypertensive patients with vitamin D deficiency. Conclusions: Vitamin D deficiency in patients with EAH is associated with severe clinical symptoms: the risk for arrhythmias increases 1.5 times [OR–2.36; p = 0.049], weakness risk increases 1.7 times [OR–2.40; p = 0.049], sleep disturbance risk elevates almost twice [OR–3.43; p = 0.005], risk for headache escalates 2.35 times [OR–3.63; p = 0.007], fatal cardiovascular risk SCORE >5.0 is 1.5 times high [OR–2.34; p = 0.046], respectively.

Objective: The aim of our study was to evaluate the role of AGT (rs4762) and GNB3 (rs5443) gene polymorphisms as risk factors for severe hypertension. Design and method: The case-control study involved 100 patients with EAH stage II, 1-3 degrees of blood pressure (BP), high and very high cardiovascular risk. Among the patients there were 21% (21) men, 79% (79) women. The mean age of patients was 59.86±6.22 y.o. The control group consisted of 60 almost healthy individuals with relevant age (49.13±6.28y.o.) and gender distribution (63% - women, 37% - men). The AGT (rs4762) gene polymorphism was studied by a qualitative polymerase chain reaction (PCR) in real time. Results: Severity of EAH does not depend on polymorphic variants of AGT (rs4762) and GNB3 (rs5443) genes. The distribution showed no statistically significant differences in the aforementioned distribution. Individuals with the first degree of hypertension met more often with the CC genotype of the GNB3 gene (rs5443) by 22.23% than among patients with the T allele (x2 = 3,66; p = 0,055) in patients with EAH. Conclusions: Epidemiological analysis did not confirm the polymorphic variants of the AGT (rs4762) and GNB3 (rs5443) genes as predictors of the severe course of EAH according to the degrees of BP elevation.

Objective: Metabolic changes and obesity play important roles in arterial hypertension pathogenesis and progression. Whereas hepatic steatosis (HS) and AH have multiple common mechanisms of development involving metabolic and immune changes, the aim of study was to investigate the influence of Pro12Ala polymorphism of PPAR-↖2 gene and I/D polymorphism of ACE gene on metabolic profile and cytokines in obese patients with HS and AH. Design and method: Study involved 154 AH patients with HS (87 males, 67 females, age 50.06±7.34). Duration of HS 1-5 years, AH 3-21 years. Metabolic disorders were defined with body mass index (BMI), glycaemia, immunoreactive insulin (IRI), total cholesterol (TC), low and high density cholesterol (LDL-C, HDL-C), triglycerides (TG), C-peptide (CP) levels and HOMA-IR index. TNF- ↑ and leptin plasma levels were assessed by ELISA. Genes’ polymorphism of PPAR-↖2 (Pro12Ala), and ACE (I/D) alone or in combination was studied with PCR. Results: Differences of BMI, plasma glucose, IRI, HOMA-IR, CP and leptin are independent from ACE gene genotypes (p>.05). Pro-allele carriers of PPAR-↖2 gene have higher BMI than AlaAla carriers (32.7±2.1 and 27.9±1.1 kg/m2 vs 25.6±0.8 kg/m2, accordingly (p<.05), leptin level – 14.3±0.41 and 8.6±0.25 ng/ml vs 3.7±0.22 ng/ml, (p<.001), glucose level – to 10.2% and 10.9% accordingly (p<.05); CP level was higher in ProPro-genotype than in Ala-allele carriers to 15.7% (p<.05). Risk group of dyslipidemia are ProPro-genotype carriers of PPAR-↖2 gene with higher level of TC, TG and LDL-C to 16.4%, 17.3% and 27.9% (p<.05) and lower level of HDL-C in women to 25.6% (p = .038). Lipids levels are independent on ACE I/D polymorphism. Baseline TNF-↑ plasma levels did not significantly deviate between genotypes of PPAR-↖2 gene, but D-allele carriers (I/D+DD) of ACE gene had higher baseline TNF-↑ plasma levels (91.61 and 109.11 pg/ml, accordingly p<.01). Conclusions: In HS hypertensive patients metabolic disorders are clearly associated with PPAR-↖2 Pro-allele (carbohydrates) and ProPro-genotype (lipids). Presence of D-allele of ACE gene is associated with reliably higher level of TNF-↑ plasma levels.