Objective. The cytochrome 11B2 aldosterone synthase gene (CYP11B2) that links to aldosterone synthase enzyme synthesis changes and blood pressure regulation is of particular interest among the renin-angiotensin-aldosterone system encoding genes.Methods. One-hundred hypertensive patients with target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Mean age was 59.87±8.02 years. Diabetes Mellitus type 2 (DM2) was in 28 persons. Chronic kidney disease (CKD) was diagnosed in 29 persons according to the National Kidney Foundation recommendations (2012) after glomerular filtration rate (GFR) decline <60 ml/min/1.73m2 for ≥3 months (measured by CKD-EPI equations). Aldosterone, cystatin-C, and creatinine levels were measured in serum. Control group included 48 practically healthy persons of relevant age. Gene’s nucleotide polymorphism CYP11B2 (-344C/T) was examined by polymerase chain reaction.Results. CKD evolution in hypertensive patients followed by higher systolic and diastolic blood pressure (SBP, DBP) values increased creatinine, cystatin-C, and aldosterone serum concentrations by 28.76%, 28.41% and 29.43% (р<0.05), respectively. Polymorphic site of CYP11B2 (rs1799998) gene is associated with SBP and DBP increase (p<0.05), reduced GFR preferably calculated by CKDEPI-cystatin C (F=10.79–14.45; p<0.001) and elevated aldosterone content (F=55.84; p<0.001), creatinine and cystatin-С as well (F=4.16–5.08; p<0.05) mainly in the ТТ-genotype female carriers (p<0.001). Hypertensive women with DM2 demonstrated stronger relations of CYP11B2 gene polymorphic site with the increased aldosterone content (F=47.52; p<0.001), than women without DM2 (p<0.001) and male patients (p=0.014).Conclusions. Genetic variations involving CYP11B2 might influence the kidney function, hypertension course, and severity via aldosterone secretion upregulation.
Objective: to evaluate the association of essential arterial hypertension (EAH) and its severity with genes polymorphism of NOS3 (rs2070744) and GNB3 (rs5443) in West-Ukrainian population. Materials and methods. One-hundred EAH patients (48 – healthy control) participated in the cohort case-control study. Blood pressure (BP), Creatinine, glucose, lipids panel were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFX96™Real-Time PCR). Risk assessed by Relative Risk, Odds Ratio and 95% Confidential intervals. Results. A mutation of the NOS3 gene (786T>C, rs2070744) and the GNB3 gene (825C>T, rs5443) in the homozygous state in the West-Ukrainian population suffers from EAH occurs with a frequency of 16.67% and 8.33%, with no differences with the control subjects (p>0.05). In both groups dominate the T-allele of the NOS3 gene and the C-allele of the GNB3 gene: in patients by 12.5% (c2=4.50; p=0.034) and 41.66% (c2=50.0; p<0.001), in the control – by 25.0% (c2=12.0; p<0.001) and 40.0% (c2=33.33; p<0.001), respectively. The results of the binary logistic regression analysis did not confirm the prediction of the EAH appearance by polymorphic variants of the NOS3 (rs2070744) and GNB3 (rs5443) genes. However, the TT genotype of the GNB3 gene (rs5443) increases unreliably the EAH risk almost twice as likely [OR=2.0; OR 95%CI:0.40-10.82; p>0.05]. Epidemiological analysis did not confirm the association of the NOS3 gene with the EAH severity. But T-allele of the GNB3 gene increases the probability of high normal BP almost 5 times [OR=4.86; OR 95%CI:0.99-24.75; p=0.042]. Conclusions: NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms are not associated with blood pressure values and EAH severity as well.
Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]. Conclusions The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands. Graphical abstract
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 the present study was to clarify the endothelial function biomarkers and carotid “intima media” thickness (IMT) changes in relation to GNB3 (rs5443) and NOS3 (rs2070744) genes polymorphism in the essential arterial hypertension (EAH). Methods. One-hundred EAH patients (48 – control) participated in the case-control study. 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. GNB3 (rs5443) and NOS3 (rs2070744) genotyping was performed by TaqMan probes (CFX96™Real-Time PCR). Results. The connection of NOS3 (rs2070744) with decreased total NO metabolites (F=71.11; p<0.001), reduced NOS3 genes transcription activity (F=8.71; p<0.001) and increased sVCAM-1 (F=6.96; p=0.002), especially in the C-allele carriers (particularly in CC-genotype patients with lower NO – 16.46% and 40.88%; p<0.001), lowered the transcription activity of NOS3 gene – 46.03% 7 times (p<0.001), and become higher sVCAM-1 – 35.48% and 89.48% (p<0.001), respectively. ANOVA did not confirm the association of GNB3 (rs5443) gene with endothelial function and carotid IMT. Severe EAH was associated with increased carotid IMT – 50.0% (p<0.001) and 57.14% (p=0.007), wider carotid arteries – 17.36% (p=0.012) and 21.79% (p=0.004), and decreased NOS3 genes transcription activity – 34.54% (p=0.003). Atherosclerotic plaques were unilateral – 24.77% (χ2=5.35; p=0.021) or bilateral – 27.62% (χ2=5.79; p=0.016). IMT---gt---0.9 mm was followed by a higher BP (p<0.001), FMD BA 11.80% decrease with compensatory increase in carotid arteries diameters – 17.38% and 21.99% (p<0.001) and sVCAM-1 by 20.49% (p=0.005). Conclusion. NOS3 (rs2070744), but not GNB3 (rs5443), gene associated with the essential arterial hypertension severity relying upon the endothelial function impairment and NOS3 genes reduced transcription activity.
Objective: More than 700 million people worldwide live with untreated essential arterial hypertension (EAH). The objective of the study was to evaluate the risks of metabolic disorders in EAH patients depending on guanine nucleotide-binding protein-↓3 subunit (GNB3, rs5443) and endothelial nitric oxide synthase (NOS3, rs2070744) genes’ allelic state. Design and method: The cohort case-control study involved 100 EAH patients (moderate-very high cardiovascular risks, aged 45-65 years) and 48 practically healthy (control). Metabolic disorders were evaluated by glucose blood value and lipids panel: total cholesterol (TC), triglycerides (TG), Low-, and High- density lipoprotein cholesterol (LDL-C, HDL-C) levels. The atherogenic index (AI) was calculated by the equation: (TC-HDL-C)/HDL-C. GNB3 (rs5443) and NOS3 (rs2070744) genotyping perfrmed by TaqMan probes in CFX96 Real-Time PCR Detection System. Results: Hyperglycemia (>6.1 mmol/l), hypertriglyceridemia (TG>1.7 mmol/l) and decreased HDL-C (<1.2 mmol/l) were relatively more common in EAH patients than in the control group by 36.11% (⇙2 = 17.88; p<0.001), 23.61% (⇙2 = 6.43; p = 0.011) and 25.0% (⇙2 = 8.32; p = 0.004) respectively. Therefore, the fasting hyperglycemia increases the EAH risk in the examined population ninefold [OR95%CI:2.86-27.08; p<0.001], hypertriglyceridemia and decreased HDL-C elevates the risk almost 3 and 3.5 times as well [OR95%CI:1.23-5.56; p = 0.009 and OR95%CI:1.46-8.71; p = 0.003], respectively. The risk of metabolic disorders (dyslipidemia and hyperglycemia) in EAH patients does not depend on NOS3 gene polymorphism (rs2070744). Contrary, in T-allele patients of the GNB3 gene (rs5443) prevailed subjects with elevated LDL-C (>3.0 mmol/l) over those with CC-genotype by 13.89% (p = 0.05). Other parameters of lipid metabolism and hyperglycemia did not differ significantly between GNB3 (rs5443) genes allelic state. However, the mutational T-allele of the GNB3 gene (825C>T) increases the risk of hyperlipidemia 8.5 times [OR 95%CI:0.99-72.70; p = 0.05] due to atherogenic LDL-C, with the protective role of CC-genotype [OR = 0.12; OR 95%CI:0.01-1.0; p = 0.048]. Conclusions: Fasting hyperglycemia, hypertriglyceridemia and lowered HDL-C, enhance the arterial hypertension risk 3-9 times (p<0.01). The polymorphic site of GNB3 (rs5443) gene, but not NOS3 (rs2070744) gene associate with hyperlipidemia in hypertensive patients.
Essential arterial hypertension (EAH) is a polygenic disease due to environmental, genetic, and epigenomic factors. The study aimed to establish the association of single nucleotide polymorphism (SNP) of AGTR1 (rs5186) and VDR (rs2228570) genes with the blood pressure (BP) elevation in EAH patients. 100 EAH subjects with hypertensive-mediated organ damaging (2nd stage), moderate, high, or very high cardiovascular risk were recruited into the case-control study. There were 70.83% females and 29.17% males, mean age 57.86±7.81 y.o. The control group included 60 healthy individuals of relevant age and gender distribution. Estimation of AGTR1 (rs5186) and VDR (rs2228570) gene polymorphism was performed by Real-Time Polymerase Chain Reaction. In EAH patients, the AGTR1 gene (rs5186) mutation occurs with a frequency of 2.78% in the absence of such among healthy individuals. The VDR (rs2228570) gene mutation occurs with a frequency of 23% cases. The C-allele carriers’ (AGTR1 gene) numbers with 2nd and 3rd BP values degree dominate over AA-genotype patients by 25.32% (χ2=4.52; р=0.033). VDR gene (rs2228570) polymorphic variants do not link to BP elevation values. Thus, the C-allele of the AGTR1 gene (rs5186) is associated with BP elevation in hypertensive patients. BP values do not depend on VDR gene (rs2228570) polymorphic variants.
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