Angiotensinogen Gene Research Articles

LINKAGE OF BODY MASS INDEX AND ANTHROPOMETRIC, LABORATORY PARAMETERS IN HYPERTENSIVE PATIENTS DEPENDING ON ANGIOTENSINOGEN (AGT, RS699) GENE POLYMORPHISM

Objective: The aim of the study was to analyze the correlations between body mass index (BMI) and clinical and laboratory parameters in patients with essential hypertension (EH) depending on angiotensinogen gene (AGT, rs699) polymorphism. Design and method: The case-control study involved 72 patients with stage II EH, 1–3 degrees of blood pressure (BP) elevation, high and very high cardiovascular risk (CVR) (29.16% men, 70.84% women). The mean age of patients was 59.87±7.98 yo. The control group consisted of 48 healthy individuals comparable in age and gender. Polymorphism of the AGT gene (rs699) was studied by polymerase chain reaction (PCR). BMI was defined as the ratio of weight to square of height (kg/m2). All enrolled/screened patients signed the Informed Consent to participate in the research. The parathyroid hormone (PTH) and vitamin 25 (OH) D levels in blood serum were determined by chemiluminescence immunoassay (MAGLUMI). Results: In TT-genotype carriers of the AGT gene (rs699) BMI was directly related to anthropometric parameters of waist circumference (WC), hip circumference (HC) and waist-hip ratio (WHR) (r = 0.70–0.81; p < 0.022), the concentration of vitamin D (r = 0.65; p = 0.043) and inversely with the blood level of ionized Ca2+ (r = -0.71; p = 0.02). Correlation matrix of laboratory, anthropometric indicators in hypertensive TC-genotype carriers showed that BMI is directly related to WC and HC (r = 0.68; p < 0.001 and r = 0.84; p < 0.001), as well as to PTH level (r = 0.43; p = 0.004), with a negative correlation with vitamin D level (r = -0.38 P = 0.011). PTH directly depends on BMI, WC and HC (r = 0.31–0.43; p < 0.042–0.004). A direct link between BMI and WC and HC was found in CC-genotype carriers (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 WHR (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 ionized Ca2+ level in the blood (r = -0.71; p = 0.02), but only in TT-genotype carriers of the AGT gene (rs699).

The effect of tannic acid on renal renin-angiotensin signaling pathway in a model of unilateral ureteral obstruction in male Wistar rats.

The purpose of current study was to elucidate polyphenol tannic acid effect on renal function and activity of the renin-angiotensin system after unilateral ureteral obstruction (UUO). Male Wistar rats were divided into three groups of six randomly: 1) Sham, 2) UUO, and 3) UUO + Tannic acid. Rats in the UUO and UUO + Tannic acid groups experienced unilateral ureteral obstruction. In the Sham group, the abdominal cavity was exposed without UUO induction. In the UUO + Tannic acid group, animals received tannic acid (20mg/kg) intraperitoneally, 6 and 12h after clamping the left ureter and 6 and 12h after the right nephrectomy. Blood samples were taken to measure blood urea nitrogen (BUN) and creatinine levels. Kidney tissue samples were obtained for assessment of oxidative stress, inflammatory indices and the levels of renin-angiotensin system components. Tannic acid administration significantly improved UUO-induced kidney dysfunction (serum BUN: 66.42 ± 14.414mg/dl, p < 0.05; serum creatinine: 1.67 ± 0.258mg/dl, p < 0.05), oxidative stress (MDA level: 95.29 ± 37.35µmol/g tissue, p < 0.05; SOD activity: 59.82 ± 13.41 U/g protein, p < 0.01) and inflammation (renal TNF-α: 57.05 ± 15.653pg/g tissue, p < 0.05; renal IL-6: 117.015 ± 24.076pg/g tissue, p < 0.001). The treatment caused a reduction in the amount of renal angiotensinogen, renin and ACE genes expression compared to the UUO group (Angiotensinogen: 8.9 ± onefold, p < 0.05, Renin: 6.5 ± 1.14 fold, p < 0.05, ACE: 4.9 ± 0.64 fold, p < 0.05). Angiotensin II type 1 receptor protein levels decreased in the tannic acid-treated rats in comparison with the UUO group (0.61 ± 0.136, p < 0.05). According to the result of the current study, tannic acid considerably attenuated the complications of unilateral ureteral obstruction through renin-angiotensin system modulation. Trial registration: IR.TUMS.MEDICINE.REC.1400.802.

Abstract 430: Epigenome Editing Of The AGT Gene As A Therapeutic Approach For Cardiovascular Disorders

Overactivation of the renin-angiotensin system contributes to many common and rare cardiovascular diseases such as hypertension, atherosclerosis, and genetic thoracic aortopathies. Current pharmacologic therapies that target this pathway have been proven safe and effective, yet they require individuals with these conditions to adhere to daily medications. CRISPR-Cas9-mediated hepatic inactivation of the angiotensinogen ( AGT ) gene, the precursor of all angiotensin peptides, could be a promising “one and done” therapeutic approach for these disorders. However, disruption of AGT by Cas9 nuclease would result in irreversible changes to the genome and would likely have negative consequences if targeted to organs outside of the liver. CRISPRoff is a CRISPR-based epigenome editing tool consisting of catalytically inactive Cas9 fused to a DNA methyltransferase, as well as a guide RNA (gRNA) designed to target a genomic promoter of interest. Targeting to a gene promoter can result in DNA methylation and subsequent silencing of gene expression, a phenomenon that has the potential to be reversed by CRISPRon, a catalytically inactive Cas9 fused to a demethylase that could be targeted to the same site using the same gRNA. We hypothesized that CRISPRoff can be used to efficiently and durably silence AGT expression by methylation of the AGT promoter. To test this, we screened HuH-7 hepatoma cells with CRISPRoff and either individual gRNAs or dual combinations of gRNAs targeting the AGT promoter. We measured AGT mRNA expression by RT-qPCR and selected the two combinations of gRNAs that resulted in the greatest decrease in AGT expression for methylation analysis. We found that AGT expression was decreased by ≈50% in treated cells, and this correlated with substantially increased methylation throughout the AGT promoter. A long-term in vitro study to assess the durability of this methylation is underway. We are also generating a humanized AGT mouse model to test whether these CRISPRoff gRNAs can silence the human AGT gene in vivo. These results provide a proof of concept of CRISPRoff for silencing of AGT expression as a therapeutic approach for common and rare cardiovascular disorders.

Angiotensin deficient FVB/N mice are normotensive.

All previous rodent models lacking the peptide hormone angiotensin II (Ang II) were hypotensive. A mixed background strain with global deletion of the angiotensinogen gene was backcrossed to the FVB/N background (Agt-KO), a strain preferred for transgenic generation. Surprisingly, the resulting line turned out to be normotensive. Therefore, this study aimed to understand the unique blood pressure regulation of FVB/N mice without angiotensin peptides. Acute and chronic recordings of blood pressure (BP) in freely-moving adult mice were performed to establish baseline BP. The pressure responses to sympatholytic and sympathomimetic as well as a nitric oxide inhibitor and donor compounds were used to quantify the neurogenic tone and endothelial function. The role of the renal nerves on baseline BP maintenance was tested by renal denervation. Finally, further phenotyping was done by gene expression analysis, histology and measurement of metabolites in plasma, urine and tissues. Baseline BP in adult FVB/N Agt-KO was unexpectedly unaltered. As compensatory mechanisms Agt-KO presented an increased sympathetic nerve activity and reduced endothelial nitric oxide production. However, FVB/N Agt-KO exhibited the renal morphological and physiological alterations previously found in mice lacking the production of Ang II including polyuria and hydronephrosis. The hypotensive effect of bilateral renal denervation was blunted in Agt-KO compared to wildtype FVB/N mice. We describe a germline Agt-KO line that challenges all previous knowledge on BP regulation in mice with deletion of the classical RAS. This line may represent a model of drug-resistant hypertension because it lacks hypotension.

Genetic Variations in Angiotensinogen Gene and Risk of Preeclampsia: A Pilot Study

Preeclampsia (PE) is a typical hypertensive disorders of pregnancy (HDP) which can cause substantial morbidity and mortality in both pregnant women and fetuses. The renin-angiotensin system (RAS) genes are the main HDP-causing genes, and Angiotensinogen (AGT) as the initial substrate can directly reflect the activity of the entire RAS. However, the association between AGT SNPs and PE risk has rarely been confirmed. This study was carried out to determine whether AGT SNPs could affect the risk of PE in 228 cases and 358 controls. The genotyping result revealed that the AGT rs7079 TT carrier was related to increased PE risk. Further stratified analysis illustrated that the rs7079 TT genotype significantly increased the PE risk in subgroups of Age < 35, BMI < 25, Albumin (ALB) ≥ 30 and Aspartate aminotransferase (AST) < 30. These findings demonstrated that the rs7079 might be a promising candidate SNP strongly associated with PE susceptibility.

Association of the ACE and AGT gene polymorphisms with global disparities in COVID-19-related deaths.

The aim of the study was to investigate the gene polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin type 1 receptor (AT1R) in association with coronavirus disease 2019 (COVID-19) mortality rates worldwide. The prevalence of ACE I/D, AGT M235T, and AT1R A1166C alleles' frequencies in different populations was assessed. Data on COVID-19-related cases and deaths were acquired from the European Center for Disease Prevention and Control, which included weekly reports by country and continent. An Excel tool was developed to visualize the acquired data of mortality and incidence by classifying them by continent/country across specific periods of time. Spearman's nonparametric correlation was used to evaluate the association between country-based frequencies in RAS gene polymorphisms and COVID-19-related deaths. While China constituted the initial reservoir of COVID-19, incidence/mortality rates in Europe and America outnumbered the figures in the former. A clear association was identified between death rates and ACE D/I ( r = 0.3659; P = 0.033), as well as AGT A/G variants ( r = 0.7576; P = 0.015). Data on AT1R polymorphisms suggested no correlation with mortality rates. Our results demonstrated a significant disparity in COVID-19-related susceptibility and mortality among different populations and corroborate the importance of gene polymorphisms in predicting and consequently improving patients' outcomes.

The Relationship between VEGF and AGT Gene Single Nucleotide Polymorphisms and Susceptibility to Renal and Bladder Cancers.

We aimed to examine the relationships between the angiotensinogen (AGT) and vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms and susceptibility to bladder and kidney cancers. A 1:1 paired case-control study was conducted, which included 143 newly diagnosed kidney cancer cases, 182 newly diagnosed bladder cancer cases, and healthy subjects in the same period collected from two hospitals. Medical records and a questionnaire were used to obtain relevant information. Genotypes were determined by improved multiple ligase detection reaction (iMLDR) and VEGF serum expression levels were detected by enzyme-linked immunosorbent assays (ELISAs). The VEGF gene/genotype frequencies of rs833061 and rs1570360 were statistically different among various pathological grades of kidney cancer, while the AGT rs699 gene/genotype frequencies were statistically different among various pathological types of bladder cancer. In kidney cancer, rs699 was associated with smoking, drinking, and hair coloring, while in bladder cancer, rs699, rs1570360, rs3025039, and rs833061 were associated with smoking, drinking, hair coloring, exercise, and urine holding. This work will help identify biomarkers that can predict the early metastasis and recurrence of kidney or bladder cancer, as well as help improve patient survival rates by predicting their susceptibility. This work will provide reference for the prevention and treatment of kidney and bladder cancers.

Angiotensinogen, Angiotensin-Converting Enzyme, and Chymase Gene Polymorphisms as Biomarkers for Basal Cell Carcinoma Susceptibility.

The intake of angiotensin-converting enzyme (ACE) inhibitors and specific antagonists of angiotensin II receptors, widely used as antihypertensive drugs, significantly reduces the risk of developing basal cell carcinoma (BCC), highlighting the possible tumorigenic role of angiotensin II (AngII). We present here the investigated genetic association between the development of BCC and functional DNA polymorphisms M235T, I/D, and A1903G in the genes of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and chymase (CMA1), which mediate AngII production levels. DNA samples of 203 unrelated Greeks were studied, including 100 patients with BCC and 103 matched healthy controls. The MT genotype of the AGT-M235T polymorphism was significantly more prevalent in the patient group (78.0%) versus the healthy control group (28.3%; p<0.001). The DD genotype of the ACE-I/D polymorphism was also increased in BCC patients (72.8%) compared to controls (46.2%; p=0.001). The heterozygous AG genotype of CMA1-A1903G was significantly more frequent in the BCC group (86%) than in the healthy controls (50.5%; p<0.001). The MT, DD, and AG genotypes of the AGT- M235T, ACE-I/D, and CMA1-A1903G polymorphisms, respectively, were significantly increased in frequency within the group of cancer patients compared to the healthy controls. All three genotypes correspond to increased enzyme levels or activity and result in increased levels of AngII; therefore, they may be potentially utilized as reliable biomarkers associated with an individual's increased risk for BCC development.

Genetic Polymorphism in Patients with Diabetic Nephropathy and Retinopathy: A Cross-sectional Study

Introduction: The chronic persistence of diabetes leads to microvascular complications, such as Diabetic Nephropathy (DN) and Diabetic Retinopathy (DR). Both of these are progressive disorders involving pathological changes in capillaries. A few biochemical pathways have been suggested to link hyperglycaemia and microvascular complications. The probability of developing and progressing DN and DR is associated with the duration of diabetes. These complex disorders are strongly influenced by both genetics and environmental factors. Several candidate genes have been reported to be associated with DN and DR in different populations. Aim: To determine the co-existence of DN and DR in relation to gene polymorphisms of Angiotensin-Converting Enzyme (ACE), Angiotensinogen (AGT), Receptor for Advanced Glycation End-products (RAGE), Aldose reductase (ALR2), and Vascular Endothelial Growth Factor (VEGF). Materials and Methods: The present DN and DR cross-sectional study was conducted at the Department of Endocrinology, University College of Medical Sciences, University of Delhi and GTB, New Delhi, India, and the Discipline of Biochemistry, Indira Gandhi National Open University, New Delhi, India. The study was conducted from October 2019 to August 2022. All the participants under uniform diabetes management were divided into two groups (100 in each group): Group 1 included Type-II diabetic patients with DN and DR, and Group 2 comprised Type-II diabetic patients with DN only. Polymorphisms in all genes were determined using Polymerase Chain Reaction (PCR), followed by digestion with restriction enzymes and visualisation through an ultraviolet transilluminator. The analysis of biochemical parameters and association of gene polymorphisms was performed using Statistical Package for Social Sciences (SPSS) version 26.0 software. Results: There were 57 males and 43 females in the DN+DR group, and 51 males and 49 females in the DN-DR group. The mean age of study subjects in the DN+DR group was 52.60±9.08 years, compared to the DN-DR group (47.33±10.68 years). The DN+DR group had a significantly higher mean duration of diabetes (11.78±6.86 vs. 5.13±4.78, p≤0.001) and a significantly lower mean waist circumference (91.30±13.99 vs. 95.11±9.95 cm, p≤0.02). The DN+DR group also had significantly higher urea (34.34±16.32 vs. 26.43±12.34 cm, p≤0.001), creatinine (1.34±0.90 vs. 0.89±0.25 cm, p≤0.03) and significantly lower estimated Glomerular Filtration Rate (eGFR) levels compared to the DN-DR group. The distribution of genotypes of ALR2 (p≤0.04) and VEGF genes (p≤0.001) showed a significant difference between both DN+DR and DN-DR groups. The frequency of the D allele of the VEGF gene (p≤0.02) (OR=1.94, 95% Confidence Interval (CI)=1.10-3.40) was higher in the DN+DR group. The DN+DR group also had a significantly lower frequency of the CT+TT dominant model of the ALR2 gene (p≤0.04) as well as an increased frequency of the ID+DD dominant model of the VEGF gene (p≤0.002). No significant differences were found in genotypic as well as allelic frequencies of ACE, AGT, and RAGE gene polymorphisms between the two groups. Conclusion: The D allele of the VEGF (I/D) gene polymorphism is significantly associated with DR in patients with DN. It can be concluded that the VEGF gene plays an important role in the development of retinopathy in DN patients.

The effects of angiotensinogen M235T/T174M and angiotensin type 1 receptor a1166c gene polymorphisms on the development of diabetic nephropathy in type 2 diabetes mellitus patients.

Diabetic nephropathy is one of the major complications of Type 2 diabetes mellitus. In this study, we aimed to investigate the effects of angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C gene polymorphisms on the development of diabetic nephropathy in patients with type 2 diabetes mellitus. This study included 100 type‑2 diabetes mellitus patients with diabetic nephropathy patients (patient group) and 99 type‑2 diabetes mellitus patients without diabetic nephropathy (control group). Polymerase chain reaction and restriction fragment length polymorphism methods were used to identify polymorphisms in the angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C genes. There was no significant difference in genotype frequencies of M235T gene polymorphism between patient and control groups (χ2 = 4.01, df = 2, p = 0.13). There was no significant difference in genotype frequencies of T174M gene polymorphism between patient and control groups (X2 = 0.36, df = 2, p = 0.83). There was no significant difference in genotype frequencies of A1166C gene polymorphism between patient and control groups (χ2 = 0.51, df = 2, p = 0.77). The results showed no significant difference in angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C gene polymorphisms between the patient and control groups. Future studies are needed to validate the results of this study and to explore underlying mechanisms (Tab. 3, Fig. 3, Ref. 35). Text in PDF www.elis.sk Keywords: type 2 diabetes mellitus, diabetic nephropathy, angiotensinogen gene polymorphism, angiotensin type 1 receptor, gene polymorphism.

Angiotensinogen Gene M235T and T174M Polymorphisms in Diabetic Nephropathy in a Bangladeshi Population

Background: Marker gene polymorphisms linked with the renin-angiotensin-aldosterone system (RAAS) have been broadly studied in diabetic nephropathy (DN) patients considering that RAAS is a potential drug target to slow down kidney disease progression. Objectives: The aim of the present study was to determine the link between M235T and T174M variants of angiotensinogen (AGT) gene and DN. Methods: A total of 93 patients with DN, mean age of 56±8 years, systolic blood pressure (SBP) of 141±14, and diastolic blood pressure (DBP) of 84±7 mm Hg (mean±SD) were investigated, among whom 59 patients had a family history of type 2 diabetes mellitus. A total of 96 healthy subjects served as the control group with no family history of diabetic nephropathy (FHDN) and type 2 diabetes mellitus, a mean age of 47±10 years, SBP of 126±11, and DBP of 76±6 mm Hg. PCR–restriction fragment length polymorphism was employed for genotyping M235T and T174M molecular variants. Results: Genotype frequencies of the variants M235T (χ2=2.038, P=0.361) and T174M (χ2=2.952, P=0.229) did not show any statistically significant association with type 2 diabetic nephropathy (T2DN) compared to the control. Based on FHDN and family history of diabetes mellitus (FHDM), the frequency of genotypes of M235T marker (P=0.360) in FHDN, and (P=0.886) FHDM; T174M marker (P=0.641) in FHDN, and (P=0.425) FHDM also did not show any statistically significant association with T2DN compared to the controls. Conclusion: M235T and T174M variants were not associated with DN in a Bangladeshi population.

Genetic Polymorphism in Angiotensinogen and Its Association with Cardiometabolic Diseases.

Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads to renal homeostasis. However, various genetic polymorphisms in AGT have been discovered in recent times which have shown an association with various diseases. Genetic polymorphism increases the level of circulating AGT in blood which exaggerates the effects produced by AGT. The associated diseases occur due to various effects produced by increased AGT levels. Several cardiovascular diseases including myocardial infarction, coronary heart disease, heart failure, hypertrophy, etc. are associated with AGT polymorphism. Other diseases such as depression, obesity, diabetic nephropathy, pre-eclampsia, and liver injury are also associated with some variants of AGT gene. The most common variants of AGT polymorphism are M235T and T174M. The two variants are associated with many diseases. Some other variants such as G-217A, A-6G, A-20C and G-152A, are also present but they are not as significant as that of M235T and T174M variants. These variants increase the level of circulating AGT and are associated with prevalence of different diseases. These diseases occur through various pathological pathways, but the initial reason remains the same, i.e., increased level of AGT in the blood. In this article, we have majorly focused on how genetic polymorphism of different variants of AGT gene is associated with the prevalence of different diseases.

Polymorphism rs7079 in miR-31/-584 Binding Site in Angiotensinogen Gene Associates with Earlier Onset of Coronary Artery Disease in Central European Population.

Angiotensinogen (AGT) represents a key component of the renin-angiotensin-aldosterone system (RAAS). Polymorphisms in the 3' untranslated region (3'UTR) of the AGT gene may alter miRNA binding and cause disbalance in the RAAS. Within this study, we evaluated the possible association of AGT +11525C/A (rs7079) with the clinical characteristics of patients with coronary artery diseases (CAD). Selective coronarography was performed in 652 consecutive CAD patients. Clinical characteristics of the patients, together with peripheral blood samples for DNA isolation, were collected. The genotyping of rs7079 polymorphism was performed with TaqMan® SNP Genotyping Assays. We observed that patients with the CC genotype were referred for coronarography at a younger age compared to those with the AA+CA genotypes (CC vs. AA+CA: 59.1 ± 9.64 vs. 60.91 ± 9.5 (years), p = 0.045). Moreover, according to the logistic regression model, patients with the CC genotype presented more often with restenosis than those with the CA genotype (p = 0.0081). In conclusion, CC homozygotes for rs7079 present with CAD symptoms at a younger age compared with those with the AA+CA genotype, and they are more prone to present with restenosis compared with heterozygotes.

Characteristic of the uncontrolled hypertension course in patients of the aral sea region with uncomplicated hypertensive crisis

Abstract Purpose To study the features of the course of uncontrolled arterial hypertension (AH) in the Aral Sea region with the identification of the prevalence of various genotypes of the angiotensinogen (AGT) gene in patients with uncomplicated hypertensive crisis. Methods The genetic part included 94 patients with uncomplicated hypertensive crisis, an average age of 55.3±8.6 years, 54 (58.3%)women and 40 men (41.7%). The control group consisted of 50 healthy women and men, an average age of 52.7±6.4 years in equal proportion. The genetic study was carried out by real-time PCR with the determination of the prevalence of genotypes and alleles of genetic polymorphisms AGT 521 C&amp;gt;T, AGT 704 T&amp;gt;C. Results Patients with uncomplicated hypertensive crisis were characterized by LV hypertrophy, thickening of the intima-media thickness of the common carotid artery, and kidney damage. Henken's test showed that patients with AH require a significantly higher concentration of table salt to determine the threshold of taste sensitivity than in the control group: 0.51±0.17% versus 0.21±0.14% concentration of NaCl. The distribution of 704T&amp;gt;C genotypes of the AGT gene polymorphism was as follows: CC genotype 43.6%, CT genotype 45.8%, TT genotype 10.6% of cases, χ2=32.777, p=0.000; C allele – 66.5%, T allele - 33.5% of cases, χ2=40.894, p=0.000. Among healthy individuals, the distribution by genotypes showed a significant predominance of the CC genotype: CC 76%, CT 24%, TT genotype was not detected in the presented sample, χ2=67.92, p=0.000; C-allele 88%, T-allele 12%, χ2=115.52, p=0.000. The above data of the group of patients and healthy people corresponded to the theoretical Hardy-Weinberg equilibrium. The distribution of 521T&amp;gt;C genotypes of the AGT gene polymorphism among AH patients was as follows: CC genotype – 79.8%, CT genotype – 16%, TT genotype – 4.2% of cases, χ2=139.8, p=0.000; C-allele – 87.8%, T-allele – 12.2%, χ2=214.5, p=0.000. Among healthy individuals, a significant predominance of the CT genotype was shown: CC genotype – 40%, CT genotype – 60% of cases, χ2=42.0, p=0.000; C-allele – 70%, T-allele – 30%, χ2=32.0, p=0.000. The above data of the group of patients and healthy people did not correspond to the theoretical Hardy-Weinberg equilibrium Conclusion Patients with uncomplicated hypertensive crisis, living in the aral sea region, are characterized by severe damage of target organs, a high threshold of taste sensitivity to table salt. Based on genetic models of inheritance, a significant prevalence of the C-allele and CC genotype 704 T&amp;gt;C AGT gene polymorphism in healthy individuals was revealed, which characterizes the C-allele and CC genotype as protective against AH in people of the Aral Sea region. Significantly greater accumulation of the C-allele 521 C&amp;gt;T polymorphism of the AGT gene among AH patients is a factor of predisposition to a complicated course of AH in people of the aral sea region. Funding Acknowledgement Type of funding sources: None.

Hipertansiyon tanısı alan hastalarda angiotensinojen (AGT) gen taraması ve nutrigenetik yaklaşımlar

ABSTRACT Aim: Today, hypertension is one of the most important preventable risk factors for diseases with fatal consequences such as stroke, heart failure, myocardial infarction, peripheral vascular disease, and end-stage renal failure, and it is estimated that there are approximately 15-16 million hypertension patients in Turkey. The aim of the study; to determine the nutritional habits of patients with clinically diagnosed hypertension and to investigate the nutrigenetic approaches of the disease. Method:For this purpose, the study is planned as two-stage. In the first stage, it was aimed to examine the nutritional habits by applying a questionnaire to the patients diagnosed with hypertension. In the second stage, it was aimed to reveal genetic changes by a screening of the Angiotensinogen gene which is the disease-related gene in the clinically diagnosed patients.. Results: In the result of the study; p.M268T change in Angiotensinogen gene was defined in one patient and this change was defined in the literature as rs699 /NCBI, which is known as one of the most important polymorphisms associated with hypertension. In addition, it was found that there was no change in nutritional patterns before and after diagnosis of hypertensive individuals and the rates of interviewing with dietitians were very low. Conclusion: The study is important as it is the first study conducted in terms of nutrigenetics in patients diagnosed with hypertension in the Turkish population.

Abstract 124: Angiotensin-(1-12) Immunoneutralization: A New Approach To Hypertension Treatment

There is a critical need to identify new therapeutic targets and treatments, given emerging data documenting the limited effectiveness of current antihypertensive drugs to have a marked impact in preventing target organ damage and cardiovascular death. While monoclonal antibodies (mAb) are revolutionizing the treatment of human diseases, including severe hypercholesterolemia, their applicability to long-term hypertension control remains unexplored. Identification of angiotensin-(1-12) [Ang-(1–12)] as a non-renin-dependent substrate for Ang II generation in rodents and humans led us to engineer a mAb directed against the C-terminus of human Ang-(1–12) [h-Ang-(1-12)] sequence. We utilized a model of hypertension expressing the human angiotensinogen (AGT) gene in the rat genome [TGR(hAGT)L1623 rats] to address the effectiveness of endogenous h-Ang-(1–12) immunoneutralization in controlling the elevated blood pressure and reversing hypertension-induced target organ damage. Acute delivery of the h-Ang-(1–12) mAb (30 mg/Kg, i.v.) in anesthetized hypertensive transgenic rats induced a prompt arterial pressure fall (M ± SE: -18 ± 6/-16 ± 3 mm Hg, n=7; p&lt; 0.001) in the absence of corresponding heart rate changes. The antihypertensive effect of the h-Ang-(1-12) mAb triggered a rise in plasma renin concentrations (from 107 ± 24 to 381 ± 260 ng/mL/h) that was inversely correlated with the fall in mean arterial pressure (r= -0.92, p&lt; 0.001). Prior intravenous delivery of aliskiren fumarate (3-5 mg/Kg, i.v.) while inducing a fall in arterial pressure did not mask the antihypertensive action of the h-Ang-(1-12) mAb. Extension of these acute effects of the h-Ang-(1-12) mAb to awake instrumented transgenic hypertensive rats given consecutive daily doses of the mAb (30 mg/Kg, i.m. x 4 -5 days, n=7) documented a trend for significant statistical drops in daytime blood pressure and no changes in heart rate. We conclude that Ang-(1–12) is an endogenous Ang II forming substrate participating in the control of arterial pressure in a humanized model of high blood pressure and that selective immunoneutralization of this alternate substrate is a promising and novel therapeutic approach to treat hypertension and prevent its adverse cardiovascular sequelae.

The effect of polymorphisms (M235T and T174M) on the angiotensinogen gene (AGT) in coronary artery disease in the Eastern Asian population: A systematic review and meta-analysis.

Background:It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is implicated in CAD susceptibility, but these results contradict those of the other studies with the associations being unclear in the Eastern Asian population. Therefore, meta-analysis was performed to evaluate this relationship.Methods:Publication databases were used to search for eligible relevant studies and valid data were extracted from studies meeting the inclusion criteria. Subsequently, odds ratios (ORs) with 95 % confidence intervals (CIs), were used to assess the strength of the association between AGT polymorphism and CAD risk.Results:Seven eligible studies published only in English were included in the present meta-analysis. In the Eastern Asian population, CAD susceptibility was shown to be related to AGT M235T under the heterozygote model (OR = 0.19). Stratified analysis indicated there was a significant relationship between AGT M235T and CAD risk in China under allelic (OR = 1.34), dominant (OR = 1.43), and heterozygote (OR = 1.62) models. The results showed that the T174M polymorphism was significantly associated with CAD risk in recessive (OR = 2.28) and homozygote (OR = 2.37) models in the Eastern Asian population.Conclusions:In the Eastern Asian population, especially the Chinese, the M235T of AGT is associated with CAD susceptibility. The T174M polymorphisms were associated with CAD risk in the Eastern Asian population.

Screening Biomarkers of Sudden Coronary Death Based on mRNA Expression Profile of Rat Myocardial Tissues.

To explore the differential expression of messenger RNA (mRNA) in myocardial tissues of rats with sudden coronary death (SCD), and to provide ideas for the forensic identification of SCD. The rat SCD model was established, and the transcriptome sequencing was performed by next-generation sequencing technology. Differentially expressed genes (DEGs) in myocardial tissues of SCD rats were screened by using the R package limma. A protein-protein interaction (PPI) network was constructed by using the STRING database and Cytoscape 3.8.2 on DEG, and hub genes were screened based on cytoHubba plug-in. Finally, the R package clusterProfiler was used to analyze the biological function and signal pathway enrichment of the selected DEG. A total of 177 DEGs were associated with SCD and were mainly involved in the renin-angiotensin system and PI3K-Akt signaling pathway. The genes including angiotensinogen (AGT), complement component 4a (C4a), Fos proto-oncogene (FOS) and others played key roles in the development of SCD. Genes such as AGT, C4a, FOS and other genes are expected to be potential biomarkers for forensic identification of SCD. The study based on mRNA expression profile can provide a reference for forensic identification of SCD.

The role of candidate gene polymorphisms for endothelial dysfunction and metabolic disorders in the development of cardiovascular diseases under the influence of production factors

Endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases. Genetic predisposition, metabolic disorders and other effects, including occupational hazards, can lead to the formation of endothelial dysfunction. The study aims to assess the role of polymorphisms of candidate genes of endothelial dysfunction and metabolic disorders in the development of cardiovascular diseases in persons with occupational pathology. Scientists have found that the carriage of certain alleles of polymorphisms G894T of the endothelial nitric oxide synthase gene, Lys198Asp and G8002A of endothelin-1, Met235Thr and Thr174Met of the angiotensinogen gene, -2548G/A, 19G/A and G2453A of leptin, 668A/G and Gln223Arg of the leptin receptor, determining the structure of proteins-markers of endothelial dysfunction and metabolic syndrome, as well as some production factors (exposure to vibration, exposure to vinyl chloride, mercury, fluorine and aluminum compounds), all these are in close connection with the development of cardiovascular diseases in persons with occupational pathology.

Prospective directions for creating a strategy for effective medicine prevention of preeclampsia (Literature review)

Preeclampsia (PE) is a main cause of morbidity and mortality for both mother and fetus. The frequency of PE is from 2 % to 8 %. The complications which are related to PE lead to more than 50,000 maternal deaths and more than 500,000 fetal deaths worldwide each year. In Ukraine, PE was diagnosed in 11,075 women in 2020 (39.32 per 1,000 births), of which severe PE was diagnosed in 1,573 women (5.58 per 1,000 births).The advances in obstetrics and neonatology have significantly mitigated many adverse pregnancy outcomes associated with PE. The optimal prevention of PE is essential to prevent the morbidity and mortality associated with this pathology. The number of researches about new management for the prevention or treatment of PE and new drugs that can affect the pathophysiology of the disease increases. The main value of potential candidates for the prevention of PE is the preclinical impact on oxidative stress, antiangiogenic factors, as well as thrombogenic potential and proinflammatory pathways of pathology development. A systematic data search was carried out in MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar and Proquest databases for 2014–2022. In this review, the results of preclinical and clinical studies about the rational prevention of the development of PE in pregnant women at risk with the involvement of the most promising drugs were analyzed. Preclinical studies have suggested new molecular targeting strategies, such as monoclonal antibodies directed against tumor necrosis factor alpha, placental growth factor, and short interfering ribonucleic acid technology to inhibit soluble fms-like tyrosine kinase-1 or angiotensinogen gene expression. Other treatment approaches that have progressed to phase III trials (either completed or ongoing) include proton pump inhibitors, metformin, nitric oxide donors and precursors, recombinant antithrombin III, digoxin immune antigen, and melatonin. There are cases suggesting that deletion of circulating soluble fms-like tyrosine kinase-1 can help to stabilize PE and prolong pregnancy.