AGTR2 Research Articles

CORRELATIONS OF BODY MASS INDEX WITH CLINICAL AND LABORATORY INDICATORS IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION DEPENDING ON AGT (RS699) GENE POLYMORPHISM

The aim. To analyze the correlations between body mass index (BMI) and clinical and laboratory parameters in patients with essential hypertension (EAH) depending on AGT gene (rs699) polymorphism. Materials and methods. The case-control study involved 72 patients with stage II EAH, 1–3 degrees of blood pressure (BP), high and very high cardiovascular risk (CVD) (29.16% (21) men, 70.84% ​​(51) women). The mean age of patients was 59.87 ± 7.98 y.o. The control group consisted of 48 healthy individuals comparable in age and gender. Polymorphism of the AGT gene (rs699) was detected by polymerase chain reaction. BMI was defined as the ratio of weight to square of height (kg/m2). Results. The correlation matrix showed a direct relationship between BMI and anthropometric parameters of waist circumference (WC), hip circumference (HC) and WC/HC ratio (r = 0.70–0.81; p ≤ 0.022), vitamin D level (r = 0,65; p = 0.043) and the reverse with the level of ionized Ca2+ in the blood (r = -0.71; p = 0.02) among TT-genotype carriers; in TC-genotype carriers BMI was directly related to WC and HC (r = 0.68; p < 0.001 and r = 0.84; p < 0.001), as well as the level of parathyroid hormone (PTH) (r = 0,43; p = 0.004), with a negative correlation with the level of vitamin D (r = -0.38; p = 0.011); in CC-genotype carriers, a direct link was found between BMI and WC and HC (r = 0.73; p < 0.001 and r = 0.78; p < 0.001). Conclusions. Thus, the correlation matrix showed that BMI directly depended on the anthropometric parameters of WC, HC and/or WC/HC (r = 0.68-0.84; p ≤ 0.022-0.001) regardless of the AGT gene genotypes (r = 0,52-0.86; p ≤ 0.02-0.001) and inversely correlated with the ionized Ca2+ level in the blood (r = -0.71; p = 0.02), but only in TT-genotype carriers of the AGT gene (rs699).

Downregulation of ACE, AGTR1, and ACE2 Genes Mediating SARS-CoV-2 Pathogenesis by Gut Microbiota Members and Their Postbiotics on Caco-2 Cells

Downregulation of ACE, AGTR1, and ACE2 Genes Mediating SARS-CoV-2 Pathogenesis by Gut Microbiota Members and Their Postbiotics on Caco-2 Cells

Potential Genes Associated with COVID-19 and Comorbidity

Hypertension, diabetes mellitus, and coronary artery disease are common comorbidities and dangerous factors for infection and serious COVID-19. Polymorphisms in genes associated with comorbidities may help observe susceptibility and disease severity variation. However, specific genetic factors and the extent to which they can explain variation in susceptibility of severity are unclear. Therefore, we evaluated candidate genes associated with COVID-19 and hypertension, diabetes mellitus, and coronary artery disease. In particular, we performed searches against OMIM, NCBI, and other databases, protein-protein interaction network construction, and GO and KEGG pathway enrichment analyses. Results showed that the associated overlapping genes were TLR4, NLRP3, MBL2, IL6, IL1RN, IL1B, CX3CR1, CCR5, AGT, ACE, and F2. GO and KEGG analyses yielded 302 GO terms (q < 0.05) and 29 signaling pathways (q < 0.05), respectively, mainly including coronavirus disease-COVID-19 and cytokine-cytokine receptor interaction. IL6 and AGT were central in the PPI, with 8 and 5 connections, respectively. In this study, we identified 11 genes associated with both COVID-19 and three comorbidities that may contribute to infection and disease severity. The key genes IL6 and AGT are involved in regulating immune response, cytokine activity, and viral infection. Therefore, RAAS inhibitors, AGT antisense nucleotides, cytokine inhibitors, vitamin D, fenofibrate, and vaccines regulating non-immune and immune factors could be potential strategies to prevent and cure COVID-19. The study provides a basis for further investigation of genes and pathways with predictive value for the risk of infection and prognosis and could help guide drug and vaccine development to improve treatment efficacy and the development of personalised treatments, especially for COVID-19 individuals with common comorbidities.

Associations between AGT M235T Polymorphism and Cancer: An Updated Meta-Analysis.

We assessed the relationship between AGT gene M235T polymorphism and the susceptibility to cancer by performing an updated meta-analysis. This study retrospectively searched related articles in the electronic databases. Afterwards, we determined combined odds ratios (ORs) and related 95% confidence intervals (CIs) by the fixed- or random-effects model. The present meta-analysis enrolled altogether 9 articles. On the whole, the relationship between AGT M235T polymorphism and the cancer risk was not significant among the entire population (TT vs. MM: OR = 1.28, 95%CI = 0.80 − 2.04; TM vs. MM: OR = 0.90, 95%CI = 0.53 − 1.52; recessive model: OR = 1.13, 95%CI = 0.83 − 1.52; dominant model: OR = 0.93, 95%CI = 0.55 − 1.57). Subgroup analysis by ethnicity, cancer type, and study quality for the relationship between the AGT M235T polymorphism and cancer risk showed no significant association. According to findings in the present meta-analysis, AGT M235T polymorphism may not be related to cancer susceptibility.

Features of the clinical course of arterial hypertension in patients with gene polymorphism under the influence of antihypertensive medicines

Arterial hypertension is a very heterogeneous disease, therefore the influence of environmental factors along with genetic factors leads to various options for the development and course of arterial hypertension. The aim of the study – to find out the effect of fixed combinations of antihypertensive drugs on the features of the clinical course of arterial hypertension in patients with gene polymorphism. We examined 86 patients. The patients were divided into 2 groups: group 1 consisted of 43 people who received a fixed combination of valsartan and amlodipine, group 2 included 43 patients who received a fixed combination of olmesartan and amlodipine. In patients of group 1, a significant decrease in average daily systolic blood pressure (SBP) in carriers of the AC genotype of the AGTR1 gene was established by 7.0% (p&lt;0.01), as well as SBP and DBP (diastolic blood pressure) in carriers of the CC genotype by 11.3 % and 9.8% (p&lt;0.01) respectively. Carriers of the TT, TC, and CC genotypes of the eNOS gene had a significant decrease in SBP by 7.8%, 8.3%, and 13.6% (p&lt;0.01), respectively, and DBP was significantly different from the indicator before treatment in carriers of the CC genotype and decreased by 11.0% (p&lt;0.02). In patients of group 2, a significant decrease in SBP in carriers of the AC genotype of the AGTR1 gene was established by 8.2 % and in DBP in carriers of the CC genotype by 11.2% (p&lt;0.01). Carriers of TT, TC and CC genotypes of the eNOS gene had a probable decrease in the level of average daily SBP by 8.3%, 9.7% and 16.5%, respectively, compared to the level before treatment (p&lt;0.01). In carriers of the CC genotype of the eNOS gene, BP decreased by 13.2% (p&lt;0.01). It has been proven that the use of fixed combinations of valsartan with amlodipine and olmesartan with amlodipine in terms of its effect on the clinical course and the level of SBP and DBP in patients with arterial hypertension with a gene polymorphism is almost the same and is most pronounced in carriers of the CC genotype of the AGTR1 and eNOS genes. Keywords: valsartan, olmesartan, amlodipine.

Geneti c Traits of Brachiocephalic Atherosclerosis

Background. According to the World Health Organization, the atherosclerosis development depends on the quality of life and lifestyle (60 %), genetic (20 %), environmental factors (10 %) and quality of medical aid (5 %). The routes to defeat atherosclerosis generally and certain systemic enzyme disorders in particular pertain in research into the population genetic predispositions to this pathology.Materials and methods.A comparative study of genetic predispositions to malignant brachiocephalic atherosclerosis analysed the renin—angiotensin system gene association in 60 patients. Th e renin—angiotensin system allelic and polymorphic loci haplotype frequencies have been determined.Results and discussion. Patients with atherosclerotic brachiocephalic vascular lesions revealed a statistically significant frequency of the AGT gene’s allele C involved in coronary heart disease development.Conclusion. Th e study suggests a putative involvement of the angiotensinogen system genes in mediating the development of brachiocephalic atherosclerosis and coronary heart disease

Modulation of Epithelial Mesenchymal Transition after AGTR-1 Gene Edition by Crispr/Cas9 and Losartan Treatment in Mammary Tumor Cell Line: A Comparative Study between Human and Canine Species.

Breast cancer is the most prevalent tumor type among women and female dogs. Tumor malignancy is characterized by the epithelial-to-mesenchymal transition (EMT) which leads to the metastasis formation. The inhibition of angiotensin II type I receptor (AGTR1) by an antagonist such as losartan can suppress angiogenesis, consequently contributing to the metastasis control. The aim of this study was to analyze the capacity of losartan and AGTR-1 gene edition to modulate the EMT process in triple negative/metastatic mammary tumor cells, compared to existing treatment protocols such as carboplatin. The cell lines CF41.Mg and MDA-MB-468, were cultured and treated with carboplatin, losartan, or submitted to AGTR-1 gene edition by CRISPR/Cas9. EMT markers and PARP-1 protein and gene expression were evaluated by immunofluorescence or immunocytochemistry and qRT-PCR, respectively. Cell migration capacity was also evaluated. For CF41.Mg and MDA-MB-468 cell lines, there was an increase in E-cadherin and a decrease in N-cadherin and PARP-1 protein and gene expression after treatment with carboplatin, losartan, both in combination and after AGTR-1 gene edition. There was a decrease in VEGF and PARP-1 protein and gene expression after AGTR-1 gene edition. Moreover, in both lines, reduction in invasion rate was observed after all treatments. Our data suggest that losartan and the gene edition of AGTR-1 by CRISPR/Cas9 were able to block the DNA repair and control the EMT process, such as carboplatin. The results in the canine species are unprecedented, as there are no data in the literature that demonstrate the action of losartan in this tumor type.

Association of angiotensinogen and angiotensin II receptor type I polymorphisms with biomarkers of carbohydrate and lipid metabolism in Dagestan residents with type 2 diabetes and hypertension

Aim. To study the associations of angiotensinogen (AGT) (s4762(С521Т), rs699(Т704C)) and angiotensin II receptor type I (AGTR1) (rs5186(A1166C)) genetic polymorphisms with serum levels of insulin, glucagon, C-peptide, leptin, as well as with dyslipidemia and glycemic levels in Dagestan residents with combination of type 2 diabetes (T2D) and hypertension (HTN), as well as with isolated T2D/HTN.Material and methods. We examined 16 patients with isolated T2D, 59 patients with T2D+HTN and 51 patients with isolated HTN from Dagestan. Genetic polymorphisms of the AGT and AGTR1 genes were studied. The levels of insulin, glucagon, C-peptide, and leptin were studied by enzyme-linked immunosorbent assay (ELISA), while lipid and carbohydrate metabolism — by biochemical methods.Results. In patients with T2D, the association of CC genotype of AGT gene rs4762(С521Т) polymorphism with a leptin decrease was determined, while its CT genotype was associated with an increase in serum level of triglycerides. The TC genotype of AGT gene rs699(Т704C) polymorphism was associated with an increase in leptin, triglyceride and glucose levels. The AA genotype of AGTR1 gene rs5186(A1166C) polymorphism was associated with an increase in insulin and glucose levels, as well as a decrease in leptin level. In patients with a combination of T2D and HTN, CC and CT genotypes of AGT gene rs4762(С521Т) polymorphism was associated with a decrease in glucagon level. The TT genotype of AGT gene rs699(Т704C) polymorphism was associated with an increase in insulin, triglyceride, glucose and body mass index (BMI) levels. In isolated HTN, the CC and CT genotypes of AGT gene rs4762(С521Т) polymorphism were associated ith a decrease in glucagon level. The TT genotype of AGT gene rs699(Т704C) polymorphism was associated with increased levels of insulin, low density lipoproteins, and BMI.Conclusion. Associations of AGT (s4762(С521Т), rs699(Т704C)) and AGTR1 (rs5186(A1166C)) genetic polymorphisms with carbohydrate and lipid metabolism changes are an important pathogenetic link of T2D and HTN, which allows developing an individual prognosis of these diseases in Dagestan residents.

Association of Lipids’ Metabolism with Vitamin D Receptor (rs10735810, rs222857) and Angiotensinogen (rs699) Genes Polymorphism in Essential Hypertensive Patients

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.

The alleles of AGT and HIF1A gene affect the risk of hypertension in plateau residents.

Plateau essential hypertension is a common chronic harmful disease of permanent residents in plateau areas. Studies have shown some single nucleotide polymorphisms (SNPs) associations with hypertension, but few have been verified in plateau area-lived people. In this paper, we examined some hypertension-related gene loci to analyze the relationship between risk SNPs and plateau essential hypertension in residents in Qinghai-Tibet plateau area. We screened hypertension-related SNPs from the literature, Clinvar database, GHR database, GTR database, and GWAS database, and then selected 101 susceptible SNPs for detection. Illumina MiSeq NGS platform was used to perform DNA sequencing on the blood samples from 185 Tibetan dwellings of Qinghai, and bioinformatic tools were used to make genotyping. Genetic models adjusted by gender and age were used to calculate the risk effects of genotypes. Four known SNPs as well as a new locus were found associated with PHE, which were rs2493134 (AGT), rs9349379 (PHACTR1), rs1371182 (CYP2C56P-PRPS1P1), rs567481079 (CYP2C56P-PRPS1P1), and chr14:61734822 (HIF1A). Among them, genotypes of rs2493134, rs9349379, and rs567481079 were risk factors, genotypes of rs1371182 and chr14:61734822 were protective factors. The rs2493134 in AGT was found associated with an increased risk of the plateau essential hypertension by 3.24-, 3.24-, and 2.06-fold in co-dominant, dominant, and Log-additive models, respectively. The rs9349379 in PHACTR1 is associated with a 2.61-fold increased risk of plateau essential hypertension according to the dominant model. This study reveals that the alleles of AGT, HIF1A, and PHACTR1 are closely related to plateau essential hypertension risk in the plateau Tibetan population.

The M235T polymorphism in the angiotensinogen gene is not a major risk factor for diabetic nephropathy; a meta-analysis

Introduction: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in diabetes patients. The angiotensin AGT M235T gene polymorphism, which is linked to the renin-angiotensin-aldosterone system (RAAS), has been extensively studied in DN patients, but the results are still conflicting. The current study’s goal is to conduct a meta-analysis to assess the relationship between AGT M235T gene polymorphism and DN susceptibility. Methods: Fourteen case-control studies related to AGT M235T polymorphism and DN were searched using PubMed, Web of Science and Google Scholar databases. Genotype data from the T2DM and T2DN groups were collected from all papers. The pooled odds ratio (OR) and 95 percent confidence interval (95% CI) were calculated employing a random-effects model to assess the relationship. Results: There were no statistically significant link between AGT M235T and DN risk in dominant (P=0.801, OR: 0.95; 95% CI: 0.66-1.38), allelic (P=0.933, OR: 1.01; 95% CI: 0.75-1.37) and recessive (P=0.374, OR: 1.21; 95% CI: 0.80-1.83) genetic models. Further, the stratified analysis based on ethnicity did not reveal significant link between AGT M235T and DN risk in Asian (Dom OR: 1.07; 95% CI: 0.63-1.82) and the Caucasian populations (Dom OR: 0.77; 95% CI: 0.49-1.21). In all three models, there was a high degree of heterogeneity between studies. Publication bias was not seen. Conclusion: Our findings suggest that the AGT gene M235T polymorphism does not contribute to DN risk. However, validation of this association will require multi-center and large population-based studies.

AGTR1 Inhibits the Progression of Lung Adenocarcinoma.

PurposeThe occurrence and development of lung adenocarcinoma (LUAD) are related to many factors. Multiple researches showed that the renin-angiotensin system (RAS) plays an important role in lung cancer. This research mainly focuses on angiotensin II receptor 1 (AT1R) encoding gene AGTR1, an important part of the RAS.MethodsWe comprehensively evaluated the expression of AGTR1 in pan-cancer based on RNA sequencing data obtained from The Cancer Genome Atlas (TCGA). We explored the correlation of AGTR1 with clinicopathological features, prognosis and tumor microenvironment in LUAD. We also explored the mechanism through enrichment analysis and verified it with cell lines and tissue samples.ResultsWe found that AGTR1 was less expressed in most tumors and related to prognosis based on the TCGA database. To further explore its mechanism, we mainly focused on LUAD. Combined with the verification results in the GEO database, AGTR1 was associated with a better prognosis in LUAD. High expression of AGTR1 was associated with less lymph node metastasis (P=0.007) and MET mutation (P=0.019). High expression of AGTR1 was related to the anti-tumor immune microenvironment with high infiltration of B cells, myeloid dendritic cells, monocytes, and low infiltration of myeloid-derived suppressor cells (all P<0.05). Enrichment analysis and in vitro verification results showed that AGTR1 was likely to play a role in LUAD through the PI3K/AKT3 pathway. Finally, we verified the above results through tissue samples and the construction of AGTR1 overexpressing cells.ConclusionAGTR1 inhibits the progression of lung adenocarcinoma through the PI3K/AKT3 pathway.

Ethnicity as a model for the development of cardiovascular diseases and their risk factors in epidemiological studies

Aim. To assess the indigenous small population of the Shor people in terms of the ethnic-specific development of cardiovascular diseases and their risk factors during the epidemiological studies in the Mountain Shoria.&#x0D; Methods. The study was carried included the indigenous and non-indigenous population of the Mountain Shoria during two different time periods: the first period (19982002) 1215 people (550 indigenous Shors and 665 non-indigenous people) and the second period (20132017) 1409 people (901 and 508, respectively). The prevalence of cardiovascular risk factors, arterial hypertension (AH) and ischemic heart disease (CHD) was studied. In the second period of the study, the genotype frequencies of the genes ACE (I/D, r 4340), AGT (c.803TC, rs699), AGTR1 (A1166C, rs5186), ADRB1 (c.145AG, Ser49Gly, rs1801252), ADRA2B (I/D, rs28365031), MTHFR (c.677CT, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) and their associations with arterial hypertension were identified. There was data on organ damage obtained among patients with high blood pressure (left ventricular myocardial hypertrophia, carotid arteries intima-media complex thickening, albumin level).&#x0D; Results. The first period of the studies showed that the Shors differed from the incoming population in an extremely low prevalence of lipid metabolism disorders, obesity, and an almost complete absence of diabetes mellitus. At the same time, there was a high prevalence of tobacco smoking and alcohol consumption. The second period of the studies demonstrated significant differences between different ethnic cohorts according to the genetic passport towards a more favorable profile among the indigenous people. However, the Shor people with arterial hypertension had a more severe course of hypertensive disease, defined as frequent organ damage. In addition, the profile of a patient with coronary heart disease differed depending on the place of residence, in urban or rural. Epidemiological studies contribute to the acquisition of new knowledge about different ethnic groups, their lifestyles and agricultural practices, regions of residence, and the features of candidate gene polymorphism. This provides valuable material for individualizing the prevention and treatment of diseases.&#x0D; Conclusion. Ethnicity makes adjustments to the patient's profile; understanding the ethnic specificity allows developing targeted preventive measures, thereby preserving the peoples health.

Associations of Gene Polymorphisms and Prognosis in Highly Adherent to Treatment Patients After Myocardial Infarction

Aim. To evaluate the influence of genetic factors on the risk of developing a combined endpoint, during a one-year supervision of patients, who had myocardial infarction and highly adherent to drug therapy.Material and methods. The research included 250 patients with high adherence to treatment with myocardial infarction, using the method of polymerase chain reaction we determined the polymorphisms Thr174Met and Met235Thr in the AGT gene, Arg389Gly and Ser49Gly in the ADRB1 gene, Ser447Ter in the LPL gene and Leu28Pro in the APOE gene, Trp212Ter and G681A in the CYP2C19 gene, and then we evaluated their influence on the prognosis.Results. A significant influence on the risk of developing combined endpoint was noticed for the polymorphism of CYP2C19 (G681A) gene. For the GA genotype of the CYP2C19 gene (G6881A), the OR of developing an unsuccessful outcome was 1.97 (95 % CI 1.05 — 3.69) (P = 0.03). For сarrier-state of A allele the OR was 1.46 (95 % CI 1.06 — 3.64) (P = 0.03). Conclusion. The results received indicate the need for individual approach for the choice of drugs from the group of inhibitors P2Y12-receptors for dual antiplatelet therapy, and if clopidogrel is chosen it is necessary to resolve the issue of pharmacogenetic testing for CYP2C19.

Association of the AGTR1 Gene A1166C (rs5186) Polymorphism with Essential Hypertension in the Indigenous Population of the Arctic

The research objective was to study the association of the AGTR1 rs5186 SNP (the A1166C variant) with essential hypertension among indigenous people of the Arctic territory of Yakutia. Methods and Results: A total of 351 participants (224 women and 127 men) were examined, including 56 Yakuts, 34 Chukchi, 77 Yukaghirs, and 184 Evens. The Case (n=168) and Control (n=183) groups were formed. Allelic variants of the AGTR1 rs5186 SNP were tested by real-time PCR. We did not find statistically significant differences in the frequency distribution of the alleles and genotypes of the AGTR1 rs5186 SNP between the Case group and the Control group. Conclusion: The obtained data show no association of the AGTR1 A1166C polymorphism with EHT in the representatives of indigenous people of the Arctic territory of Yakutia.

Indicators of the molecular pathogenesis of virulent Newcastle disease virus in chickens revealed by transcriptomic profiling of spleen

Newcastle disease virus (NDV) has caused significant outbreaks in South-East Asia, particularly in Indonesia in recent years. Recently emerged genotype VII NDVs (NDV-GVII) have shifted their tropism from gastrointestinal/respiratory tropism to a lymphotropic virus, invading lymphoid organs including spleen and bursa of Fabricius to cause profound lymphoid depletion. In this study, we aimed to identify candidate genes and biological pathways that contribute to the disease caused by this velogenic NDV-GVII. A transcriptomic analysis based on RNA-Seq of spleen was performed in chickens challenged with NDV-GVII and a control group. In total, 6361 genes were differentially expressed that included 3506 up-regulated genes and 2855 down-regulated genes. Real-Time PCR of ten selected genes validated the RNA-Seq results as the correlation between them is 0.98. Functional and network analysis of Differentially Expressed Genes (DEGs) showed altered regulation of ElF2 signalling, mTOR signalling, proliferation of cells of the lymphoid system, signalling by Rho family GTPases and synaptogenesis signalling in spleen. We have also identified modified expression of IFIT5, PI3K, AGT and PLP1 genes in NDV-GVII infected chickens. Our findings in activation of autophagy-mediated cell death, lymphotropic and synaptogenesis signalling pathways provide new insights into the molecular pathogenesis of this newly emerged NDV-GVII.

Assessment of calcium antagonist therapy protective effect on the thickness of the intima-media complex in patients with arterial hypertension

Aim. To evaluate the connection of calcium antagonist (amlodipine) therapy with the dynamics of the intima-media complex thickness in patients with arterial hypertension (AH), depending on genetic polymorphism.Methods. The study included representatives of the indigenous nationality (the Shors) – 901 people, of which a group of 367 people with hypertension was identified. The prospective stage of observation included 234 people who did not receive antihypertensive therapy. Based on the prescription of calcium antagonists, patients with hypertension were divided into two groups. Gene polymorphism was tested by polymerase chain reaction.Results. In the Shor cohort, the regression of the intima-media complex thickness of the carotid arteries was observed more often in hypertensive patients who received calcium antagonists if to compare them with those who did not take the drug [OR = 2.30]. In addition, the decrease in the atherosclerotic process is associated with the genotype carriage: I/I of the ACE gene [OR = 9.42], T/C of the AGT gene [OR = 3.52], 4b/4b and 4b/4a of the eNOS gene [OR = 2.26 and OR = 3.75], C/C of the MTHFR gene [OR = 2.62].Conclusion. Pharmacogenetic aspects are valuable from the point of view of an individual approach and obtaining the most pronounced pharmacological response in order to slow down the processes of vascular wall remodeling in patients with hypertension.

Salt-contaminated water inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in broilers.

NaCl is the main component of freshwater salinization. High NaCl concentration in drinking water can cause pulmonary hypertension syndrome (PHS) and kidney damage in broilers. To explore the effect of NaCl in drinking water on broilers' kidneys, this study divided 80 chickens into four groups. With the control group fed with pure water, broiler chickens were fed with fresh water (FW, NaCl 1 g/L), low salt-contaminated water (L-SCW, NaCl 2.5 g/L), and high salt-contaminated water (H-SCW, NaCl 5 g/L). The results show that ascites heart index (AHI) and hematocrit (HCT) of broilers increase in L-SCW and H-SCW, the serum blood urea nitrogen and creatinine of broilers increase significantly, the kidney index increases, the kidney sections show vacuolar degeneration and fibrotic degeneration, and the TUNEL results show that the kidneys possess obvious apoptosis. In addition, the detection of RAAS-related genes (AGT gene in the liver, REN in the kidney, ACE in the lung) demonstrates that after using salt-contaminated water, the transcription levels of AGT, REN, and ACE rise significantly, and the concentration of angiotensin II (Ang II) also increases significantly. In order to verify the effect of Ang II on broiler kidneys, this research used exogenous Ang II to treat chicken embryonic kidney (CEK) cells. The results show that the cell activity of CEK decreased with the increase of the concentration of exogenous Ang II. Meanwhile, the flow cytometry assay shows that Ang II could promote the apoptosis of CEK cells. These results indicate that the salt-contaminated water can aggravate PHS and cause kidney damage. The mechanism may be related to the increase of Ang II.

Polymorphic variants of ACE, AGT, AGTR1, MTHFR and NOS3 candidate genes connected with arterial hypertension as part of the metabolic syndrome among the shor people

Background: The problem of high blood pressure in the framework of metabolic syndrome (MS) is one of the most important for modern medicine in connection with the predicted increase in the incidence in the future and an increase in the mortality rate from cardiovascular disease.Aims: the aim of the study is to examine the frequency of arterial hypertension (AH) as part of the MS among the members of the indigenous population of the Mountain Shoria and to state the degree of the interconnection between the expression level of the candidate genes ACE, AGT, AGTR1, MTHFR and NOS3 and certain health problem.Materials and methods: The sample included 901 members of the indigenous population living in the settlements of the Mountain Shoria region. All experimental subjects had their blood pressure measured, anthropometry (measurements of height, body weight, waist circumference) taken according to standard procedures, fasting blood taken to determine the lipid spectrum and glucose level, morning urine dose taken and albumin level detected. All the patients with hypertension underwent duplex scanning of the brachycephalic arteries and examination of the structural and functional state of the myocardium was performed using echocardiography. Gene polymorphisms ACE (I/D, rs4340), AGT (c.803T&gt;C, rs699), AGTR1 (A1166C, rs5186), MTHFR (c.677C&gt;T, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction.Results: Among the indigenous population of the Mountain Shoria, the frequency of hypertension combined with abdominal obesity and any other additional component of MS was 28.2%. In the group of the patients with, organ changes in the form of left ventricular myocardial hypertrophy and an increase in the thickness of the intima-media complex were more common than in the group of patients with AH alone: 58.0% versus 45.1%, p = 0.029 and 81.9% versus 67 , 0%, p = 0.007, respectively. The high risk of hypertension within the framework of MS was determined by the D allel of the ACE gene [OR = 2.45; 95% CI (1.05-5.72)].Conclusions: The high frequency of the spread of high blood pressure within MS confirms that hypertension is less frequently manifested as an isolated disease, more often combined with other components of MS — abdominal obesity or disorders of carbohydrate and lipid metabolism. Stated genetic predisposition to hypertension within the MS in a specific small cohort of the Shors will undoubtedly help in the development and implementation of the health programs.

Связь полиморфных вариантов генов-кандидатов АСЕ, AGT, AGTR1, MTHFR и NOS3 с артериальной гипертензией в рамках метаболического синдрома в коренной малочисленной популяции шорцев

Background: The problem of high blood pressure in the framework of metabolic syndrome (MS) is one of the most important for modern medicine in connection with the predicted increase in the incidence in the future and an increase in the mortality rate from cardiovascular disease. Aims : the aim of the study is to examine the frequency of arterial hypertension (AH) as part of the MS among the members of the indigenous population of the Mountain Shoria and to state the degree of the interconnection between the expression level of the candidate genes ACE, AGT, AGTR1, MTHFR and NOS3 and certain health problem. Materials and methods : The sample included 901 members of the indigenous population living in the settlements of the Mountain Shoria region. All experimental subjects had their blood pressure measured, anthropometry (measurements of height, body weight, waist circumference) taken according to standard procedures, fasting blood taken to determine the lipid spectrum and glucose level, morning urine dose taken and albumin level detected. All the patients with hypertension underwent duplex scanning of the brachycephalic arteries and examination of the structural and functional state of the myocardium was performed using echocardiography. Gene polymorphisms ACE (I/D, rs4340), AGT (c.803T>C, rs699), AGTR1 (A1166C, rs5186), MTHFR (c.677C>T, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction. Results: Among the indigenous population of the Mountain Shoria, the frequency of hypertension combined with abdominal obesity and any other additional component of MS was 28.2%. In the group of the patients with, organ changes in the form of left ventricular myocardial hypertrophy and an increase in the thickness of the intima-media complex were more common than in the group of patients with AH alone: 58.0% versus 45.1%, p = 0.029 and 81.9% versus 67 , 0%, p = 0.007, respectively. The high risk of hypertension within the framework of MS was determined by the D allel of the ACE gene [OR = 2.45; 95% CI (1.05-5.72)]. Conclusions: The high frequency of the spread of high blood pressure within MS confirms that hypertension is less frequently manifested as an isolated disease, more often combined with other components of MS — abdominal obesity or disorders of carbohydrate and lipid metabolism. Stated genetic predisposition to hypertension within the MS in a specific small cohort of the Shors will undoubtedly help in the development and implementation of the health programs.