The study aim was to analyse the frequency of polymorphic variants of angiotensinogen gene polymorphism (AGT 704T>C, rs699) in essential arterial hypertension (EAH) patients. METHODS: Seventy-two individuals with EAH and hypertension-mediated organ damage (stage 2), moderate, high or very high cardiovascular risks were involved in the case-control study. Among them, 70.84 % (51) were females and 29.16 % (21) were males; mean age was 59.87±7.98 y. The control group consisted of fi fty practically healthy individuals at relevant age (49.13±6.28 y) and with relevant sex distribution (62 % were females, 38 % were males). AGT (704T>C) gene polymorphism was examined by RT-PCR. RESULTS: The distribution of genotypes in the study group was as follows: TT -14 %, TC -60 %, CC -26 %, which corresponded to the distribution in the control group -16 %, 54 % and 30 %, respectively, and did not deviate from the Hardy-Weinberg equilibrium. Smoking, type 2 diabetes mellitus (DM2) and obesity increased the relative risk of EAH in the examined population 2.5 times [OR=2.81; p=0.049], 3.75 times [OR=4.68; p=0.005] and almost twofold [OR=2.90; p=0.004], respectively. The probability of EAH increases fourfold with the angiotensin II elevation in the serum. Genotypes and alleles of the AGT (704T>C) gene were not signifi cant risk factors for EAH and DM2 in the studied population. However, the TC-genotype (lesser T-allele) increases the risk of obesity in EAH patients more than 1.5 times [OR=2.93; p=0.03]. In addition, the T-allele increases the risk for blood pressure (BP) to elevate up to grade 2-3 [OR=3.64; p < 0.001]. CONCLUSIONS: One-way ANOVA analysis confi rmed the AGT (704T>C) gene polymorphism to be associated with systolic and diastolic BP elevation (F=7.80; p < 0.001 and F=4.90; p=0.01, respectively), especially in TT-genotype carriers (p < 0.05), and with body mass index increase, albeit only in women (F=13.94; p < 0.001) (Tab. 4, Fig. 3, Ref. 26).

BACKGROUND: Cardiovascular (CV) diseases are the most spread cause of mortality in the world. Essential arterial hypertension (EAH), as a major risk factor for the development of CV diseases, is a multifactorial disease involving environmental and genetic factors together with risk-conferring behaviors. AIM: The purpose of this study was to analyze lipid metabolism changes in patients with EAH depending on the Vitamin D receptor (VDR rs2228570 (aka rs10735810)) and angiotensinogen (AGT rs699) genes polymorphism. MATERIALS AND METHODS: The single-stage study involved 100 patients suffering from Stage 2 EAH, 1–3 degrees of blood pressure increase, high and very high CV risks, 21% (21) men, and 79% (79) women. The average age of patients was 59.86 ± 6.22 years old. The control group included 60 practically healthy individuals of an appropriate age and sex distribution. To examine the VDR gene (rs10735810, rs2228570) and AGT gene (rs699) polymorphism, a qualitative real-time polymerase chain reaction was made. The lipid metabolism was studied by determining the blood plasma content of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs). RESULTS: Т allele of AGT gene is associated with reduced HDL-C level in men and increased TGs level in women. The EAH risk increases 4.5 times as much among the ТС-genotype carriers and lowered HDL-C level (odds ratio [OR] = 6.43; p = 0.01). The EAH risk increases as far as the HDL-C level reduction, irrespective of the VDR gene alleles condition 1.83 times (OR = 2.37; OR 95% confidence interval [CI]: 1.02–5.51; p = 0.04) and 1.9 times (OR=2.43; OR 95% CI: 0.99–5.97; p = 0.04). HDL-C reduction and LDL-C elevation in women increase the EAH risk 2.4 times (OR = 3.27; p = 0.01) and 1.24 times (OR = 3.67; p = 0.01), respectively. CONCLUSIONS: The EAH risk increases with a reduced HDL-C level in the TC genotype carriers of the AGT gene and irrespective of VDR gene polymorphic variants.

Objective:Hypertension and dyslipidemia represent two of the most relevant modifiable cardiovascular risk factors and they often coexist. The aim of the research was to study lipid disorders and essential arterial hypertension (EAH) risk depending on AGTR1 (rs5186) and VDR (rs2228570) genes polymorphism.Design and method:100 subjects with EAH and target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Among them, 70,83% females and 29,17% males, mean age 57,86 ± 7,81y.o. Control group consisted of 60 practically healthy individuals of relevant age. The lipid panel parameters, such as: TC (Total cholesterol), TG (Triglycerides), LDL-C (Low-density lipoprotein cholesterol), HDL-C (High-density lipoprotein cholesterol) were investigated in blood plasma, using diagnostic kits “Accent 200” (Poland). The atherogenic index (IA) was calculated by the formula: (TC – HDL-C)/ HDL-C. Gene polymorphism of AGTR1 (rs5186) and VDR (rs2228570), was detected by polymerase chain reaction (PCR).Results:Decreased HDL-C is associated with 2nd and 3d degrees of EAH (p = 0,048). The risk of EAH increases in C-allele carriers of AGTR1 (rs5186) gene with hypercholesterolemia (TC> 5,0mmol/l) 1,5 times (OR–2,50;p = 0,048), with an increase in LDL-C and IA – 1,58 and 2,12 times (OR–10,80;p = 0,019), respectively. Homozygous carriers of the minor A-allele had extremely higher concentrations of TC, atherogenic LDL-C and IA, than GG-carriers – by 9,29%, 11,11% and 12,80% (pAA<0,05), respectively. Risk of EAH increases with hypertriglycerolemia 1,89 times (OR–2,93;p = 0,03) and with the increase in LDL-C – 1,26 times (OR–3,60;p = 0,038) in AA-genotype carriers of VDR (rs2228570) gene. Risk of EAH synergistically escalates almost twice in A-allele carriers of VDR (rs2228570) gene with a decrease of HDL-C (OR–2,88;p = 0,046) and the increase of IA (OR–2,70;p = 0,039), significantly only in AG-carriers though. ANOVA analysis confirmed the association of VDR (rs2228570) gene with the increase in IA (F = 3,80;p = 0,05).Conclusions: The EAH risk escalates with hypercholesterolemia, elevated both LDL-C and IA in C-allele carriers of AGTR1 (rs5186) gene, as well as with decreased HDL-C and increased IA in A-allele carriers VDR (rs2228570) in the observed.

Objective. To determine the phenotypic manifestations of essential arterial hypertension (EAH) according to the vitamin D receptor gene polymorphism (VDR rs10735810, rs2228570).Material and methods. The case-control study involved 100 patients with EAH stage II, 1-3 degrees of blood pressure (BP), high and very high cardiovascular risk, 21% (21) men, 79% (79) women. The mean age of patients was 59.86 ± 6.22 y.o. The control group consisted of 60 healthy individuals, comparable in age and gender. To study the VDR gene polymorphism (rs10735810, rs2228570) performed a qualitative polymerase chain reaction in real-time. Results. Almost half of the patients with elevated normal BP (44.4%) and 34% of patients with EAH 2-3 d. there is concomitant diabetes mellitus (DM) type 2, while for EAH 1 d. it is only 19%. Obesity of 1-3 degrees was shown in 53% of patients with EAH: average EAH of 1 d. - 21%, among the EAH 2-3 d. - 25%. In the control group, 16% suffered from obesity. The distribution of VDR gene polymorphism genotypes according to the presence of DM showed that it was present in 35% of patients with AA-genotype, which is 1.6 times more often than in patients with GG-genotype (22%). Most smokers among patients with GG-genotype (26%), which is twice as common as those with AA- and AG-genotype (13% and 14%, respectively). Obesity of 1-3 degrees most often met among carriers of GG-genotype - 74%, and in the control group 14%. An elevated level of waist-hip ratio (WHR) among women with EAH was in 80% of the AA-genotype carriers, in the control group, all women had normal values. In 76% of the AG-genotype carriers and in 81% of the GG-genotype carriers, the WHR was increased by 2.3 and 2.8 times, respectively, that in the control group. Deviations of systolic and diastolic BP according to the VDR gene polymorphic variants have not been established.Conclusions. The AA-genotype is associated with DM 2 and with elevated WHR in women; GG-genotype - with elevated BMI, especially in men.

Objective:Primary/essential hypertension (PH) is the most common cause of left ventricular hypertrophy (LVH) and is often associated with metabolic disorders. The aim of the study was to analyse dependence of metabolic parameters on the guanine nucleotide binding protein (G-protein) 3 subunit gene polymorphism (GN3, rs5443) in hypertensive patients.Design and method:A cross-sectional study involved 72 PH patients of high and very high cardiovascular risk (29.16% men and 70.84% women); the average age 59.87 ± 7.98 y. The control group included 48 healthy individuals (aged 49.13 ± 6.28 y) and sex distribution (62.5% women and 37.5% men). GN3 (C825T) polymorphism was investigated by Real Time PCR. LVH was assessed by EchoKG. Metabolic disorders were studied by lipids panel (Total cholesterol (TC), Triglycerides (TG), Low-, and High- density lipoprotein cholesterol (LDL-C, HDL-C) levels) and Glucose blood value. The atherogenic index (AI) was calculated by the formula: (TC – HDL-C)/ HDL-C.Results:In CC-genotype carriers of the GN3 gene metabolic parameters were as follows: TC 5.50 ± 0.79 mmol/L, TG 2.10 ± 0.8 mmol/L, HDL-C 1.22 ± 0.22 mmol/L, LDL-C 4.03 ± 0.76 mmol/L, AI 3.66 ± 0.84 U, Glucose 7.7 ± 2.34 mmol/L. In PH patients with TC-genotype the concentration of TC was 5.82 ± 1.15 mmol/L (pCC>0.05), TG 1.73 ± 0.55 mmol/L (pCC> 0.05), HDL-C 1.30 ± 0.21mmol/L (pCC> 0.05); LDL-C 4.39 ± 1.07 mmol/L (pCC> 0.05), AI 3.61 ± 0.95 (pCC> 0.05), Glucose 7.37 ± 2.34 mmol/L (pCC> 0.05). In TT-genotype carriers the concentration of TC was 6.6 ± 0.64 mmol/L (it was higher than in C-allelle carriers by 20.0% (pCC> 0.05) and 13.79% (pTC = 0.016) as much), TG – 2.6 ± 1.27 mmol/L, that was higher than in C-allelle patients by 23.81% (pCC> 0.05) and 52.94% (pTC = 0.038), respectively. The other parameters did not differed significantly between genotypes’ carriers and in mutation homozygous T-allele carriers were as follows: HDL-C 1.3 ± 0.05 mmol/L (pCC, TC> 0.05), LDL-C 4.7 ± 0.69 mmol/L (pCC, TC> 0.05), AI 4.0 ± 0.69 (pCC, TC> 0.05), Glucose 6.20 ± 1.2 mmol/L (pCC,TC> 0.05).Conclusions:Therefore, the metabolic disorders in hypertensive patients do not depend on the GN3 (rs5443) gene polymorphism.

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 the study was to analyze metabolic and hormonal parameters changes in patients with essential arterial hypertension (EAH) depending on the vitamin D receptor gene (VDR, rs2228570) polymorphism. Design and method: The study involved 100 patients suffering from EAH with target-organ damaging, moderate, high or very high cardiovascular risk. Among them were 79.0% (79) women and 21.0% (21) men, an average age was 59.87±8.02 yo. The control group involved 60 practically healthy persons, matched by age and gender distribution. All enrolled/screened patients signed the Informed Consent to participate in the research. The VDR gene (rs2228570) polymorphism was studied by a real-time polymerase chain reaction (RT-PCR) method. The intact parathyroid hormone (intact PTH) and vitamin 25 (OH) D levels in blood serum were determined by chemiluminescence immunoassay (MAGLUMI). Results: The decreased level of vitamin 25 (OH) D (<30 ng/ml) was found more often in the A-allele carriers of the VDR gene (rs2228570), than in GG-genotype carriers: in the control group - by 36.84% (x2 = 10.32; p = 0.001), in study group - by 42.42% (x2 = 39.27; p<0.001). Hypocalcemia according to the level of ionized blood calcium (Ca2+ <1.12 mmol/l) was registered only in G-allele carriers, both among practically healthy and hypertensive patients. In the control group, GG-genotype carriers had a lower ionized Ca2+ blood level with a compensatory higher concentration of the intact PTH in comparison with A-allele carriers - by 3.42%, 25.19% and 16.03% (p<0.05), respectively. Secondary hyperparathyroidism due to a compensatory increasing of the intact PTH (>65 pg/ml) was found more often in the G-allele carriers of the VDR gene (rs2228570) than in AA-genotype carriers: in control group - by 55.55% (x2 = 11.11; p<0.001), and in the group of patients with EAH - by 62.5% (x2 = 12.5; p<0.001). Conclusions: The GG-genotype of the VDR gene (rs2228570) increases the risk of hypocalcemia by more than 6 times [OR = 6.25; 95% CI: 1.05-37.37; p = 0.046], with the lowest probability in carriers of the A-allele [OR = 0.16; 95% CI: 0.03-0.96].

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.