AGTR2 Research Articles

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>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.

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.

Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

Distribution of Polymorphic Marker of Genes of the Renin-angiotensin System RAS (AGT, AGTR1, АСЕ), ITGB3, PPARG) in Pa-tients With Essential Arterial Hypertension Depending on the Nature of the Nocturnal De-crease of BP

A clinical-genetic study using ABPM (24-hour BP monitoring) and Holter’s ECG methods in 49 pa-tients with essential arterial hypertension (group 1: 17 patients without sufficient nocturnal BP de-crease СI≤10%, and group 2: 32 patients with suf-ficient nocturnal BP decrease СI≥10%,) was per-formed for comparative analysis of the genotype frequencies of ACE, AGT, AGTR1, ITGB3, and PPARG. The study was conducted in order to clari-fy the pathogenetic mechanisms of the implementa-tion of different dynamics of nocturnal blood pres-sure in patients with hypertension without metabol-ic syndrome. It was found that in group 1, protec-tive genotype II of the ACE gene was more com-mon (p ≤ 0.025) than in the population data. A sig-nificant increase (p ≤ 0.025) in the frequency of the CC genotype of the AGTR1 gene responsible for the formation of insulin resistance compared to the population data was combined with a significant increase in the frequency of autonomic dysfunction in patients of group 1 - 83.4% vs. 64.5% group 2 respectively. The results obtained indicate the pos-sible pathogenetic links between genetically deter-mined insulin resistance and autonomic nervous system dysfunction and allows us to determine therapeutic approaches for correcting the noctur-nal blood pressure profile.

Rare and intractable fibrodysplasia ossificans progressiva shows different PBMC phenotype possibly modulated by ascorbic acid and propranolol treatment.

Fibrodysplasia Ossificans Progressiva (FOP) is a rare congenital intractable disease associated with a mutation in ACVR1 gene, characterized by skeleton malformations. Ascorbic acid (AA) and propranolol (PP) in combination is reported to minimize flare-ups in patients. FOP leukocyte phenotype may possibly be modulated by AA and PP treatment. In this study, expression of 22 potential target genes was analyzed by RT-PCR in peripheral blood mononuclear cells culture (PBMC) from FOP patients and controls to determine effectiveness of the combination therapy. PBMC were treated with AA, PP and AA+PP combination. Basal expression of 12 of the 22 genes in FOP PBMC was statistically different from controls. ACVR1, ADCY2, ADCY9 and COL3 were downregulated while COL1 was upregulated. ADRB1, ADRB2, RUNX2, TNF-α and ACTB, were all overexpressed in FOP PBMC. In control, AA upregulated COL1, SVCT1, ACTB, AGTR2 and downregulated ADCY2. In FOP cells, AA upregulated ACVR1, BMP4, COL1, COL3, TNF-α, ADCY2, ADCY9, AGTR2 and MAS, while downregulated ADBR2, RUNX2, ADCY1, SVCT1 and ACTB. PP increased ADBR1 and decreased RUNX2, TNF-α, AGTR1, ACTB and CHRNA7 genes in treated control PBMC compared to untreated. PP upregulated ADBR1, ADBR2 and MAS, and downregulated TNF-α and ACTB in treated FOP PBMC versus untreated. AA+PP augmented ADRB1 and ADRB2 expressions in control PBMC. In FOP PBMC, AA+PP augmented ACVR1, COL1, COL3, ADBR1, AGTR2 and MAS expression and downregulated ADBR2, RUNX2, ACTB and MRGD. These data show distinct gene expression modulation in leukocytes from FOP patients when treated with AA and or PP.

Этно-территориальное распределение мутаций C174M и C235T гена AGT и C677T гена MTGFR среди населения Азербайджанской Республики

The prevention of hereditary diseases associated with gene and chromosomal disorders, in particular multifactorial-polygenic diseases is one of actual areas of medical genotyping. For the first time in the population of the Republic of Azerbaijan we have identified mutations C174T and C235T of the angiotensinogen gene and mutation C677T of the methylenetetrahydrofolate reductase gene both in the control group and among patients with diseases of the cardiovascular system. Reliable connections for the frequency of occurrence of polymorphism of the C174T and C235T alleles of the angiotensinogen gene and polymorphism of the C677T allele of the methylenetetrahydrofolate reductase gene were found with a statistical method. To identify the ethno-geographic relationship of the mutations C174T and C235T of the AGT gene for the population of the Azerbaijan Republic, we examined practically healthy individuals and patients with CVD. The composition of this group was multinational and corresponded to the main national and ethnic composition of the Republic. The distribution of the identified mutations C174T and C235T of the AGT gene, as well as the C677T polymorphism of the MTHFR gene among ethnic groups of the Azerbaijan Republic is identified as uneven.

Polymorphism of ACE, AGT, AGTR1 genes as genetic predictors of hypertension

The genetic architecture of blood pressure (BP) includes more than 30 genes, the polymorphic variants of which cause phenotypic heterogeneity of BP. Given that a human genetic information is largely stable from birth, it can act as an early predictor of hypertension (HTN). Identification of polymorphic variants of genes associated with a high HTN risk may be one of the promising areas of early diagnosis and prevention of this disease. In addition, the availability of this data will make it possible to clarify the prognosis of patients already with HTN, as well as to personalize the treatment approach. The review analyzes the papers devoted to the molecular genetic basis of hypertension and identifies the possible role of gene polymorphism of the renin-angiotensin-aldosterone system in hypertension development. A large number of studies have revealed an association between HTN and polymorphic variants of the ACE, AGT, AGTR1 genes. In addition, polymorphism of these genes is involved in the development of atherosclerosis and related diseases, kidney and central nervous system disorders, and justifies the effectiveness of angiotensin-converting enzyme inhibitors in the treatment of HTN.

Correlation Networks Provide New Insights into the Architecture of Testicular Steroid Pathways in Pigs.

Steroid metabolism is a fundamental process in the porcine testis to provide testosterone but also estrogens and androstenone, which are essential for the physiology of the boar. This study concerns boars at an early stage of puberty. Using a RT-qPCR approach, we showed that the transcriptional activities of several genes providing key enzymes involved in this metabolism (such as CYP11A1) are correlated. Surprisingly, HSD17B3, a key gene for testosterone production, was absent from this group. An additional weighted gene co-expression network analysis was performed on two large sets of mRNA-seq to identify co-expression modules. Of these modules, two containing either CYP11A1 or HSD17B3 were further analyzed. This comprehensive correlation meta-analysis identified a group of 85 genes with CYP11A1 as hub gene, but did not allow the characterization of a robust correlation network around HSD17B3. As the CYP11A1-group includes most of the genes involved in steroid synthesis pathways (including LHCGR encoding for the LH receptor), it may control the synthesis of most of the testicular steroids. The independent expression of HSD17B3 probably allows part of the production of testosterone to escape this control. This CYP11A1-group contained also INSL3 and AGT genes encoding a peptide hormone and an angiotensin peptide precursor, respectively.

Hypertension in African Populations: Review and Computational Insights.

Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.

Common genetic variants and pathways in diabetes and associated complications and vulnerability of populations with different ethnic origins

Diabetes mellitus is a complex and heterogeneous metabolic disorder which is often pre- or post-existent with complications such as cardiovascular disease, hypertension, inflammation, chronic kidney disease, diabetic retino- and nephropathies. However, the frequencies of these co-morbidities vary among individuals and across populations. It is, therefore, not unlikely that certain genetic variants might commonly contribute to these conditions. Here, we identified four single nucleotide polymorphisms (rs5186, rs1800795, rs1799983 and rs1800629 in AGTR1, IL6, NOS3 and TNFA genes, respectively) to be commonly associated with each of these conditions. We explored their possible interplay in diabetes and associated complications. The variant allele and haplotype frequencies at these polymorphic loci vary among different super-populations (African, European, admixed Americans, South and East Asians). The variant alleles are particularly highly prevalent in different European and admixed American populations. Differential distribution of these variants in different ethnic groups suggests that certain drugs might be more effective in selective populations rather than all. Therefore, population specific genetic architectures should be considered before considering a drug for these conditions.

THE ROLE OF GENES COMBINATION IN ESSENTIAL ARTERIAL HYPERTENSION

Abstract Objective: The aim of the study was to analyze the association of AGT (T704C) and VDR (1056T/C) genes polymorphisms combination with essential hypertension (EH). Design and method: The study involved 100 patients suffering from PAH with target-organ damaging, moderate, high or very high cardiovascular risk. Among them there were 79.0% (79) women and 21.0% (21) men, average age 59.87 ± 8.02 yo. The control group involved 30 practically healthy persons, matched by age (43.36 ± 7.1 y) and gender (62.5% women, 37.5% men). All enrolled / screened patients signed the Informed Consent to participate in the research. The genes polymorphism AGT (704 T > C) and VDR (1056T/C) was studied with PCR based method. Results: The genotypes distribution of the AGT (704T > C) and VDR (1056T/C) genes genotypes in patients vs control group did not differ reliably and was as follows: for AGT gene TT-, TC- and CC –genotypes - 13.89% vs 16.67%, 59.72% vs 54.17% and CC-genotype - 26.39% vs 29.17%; for VDR gene AA-, AG-, GG-genotypes – 23.0% vs 30.0%, 50.0% vs 46.67%, 27.0% vs 23.33% (p > 0.05) accordingly. Distribution of polymorphic variants of both genes corresponded to the Hardy-Weinberg Equilibrium (p > 0.05). The distribution of mutant genotypes combinations of both genes in study and control groups was as follows: TC + AG - 31.94% vs 29.17% (p > 0.05), TC + GG – 16.67% vs 8.33% (p > 0.05), TT + AG – 8.33% vs 4.17% (p > 0.05), TT + GG – 4.17% vs 8.33% (p > 0.05). The polymorphic variant combinations of both genes don’t influence the risk of EH in observed population. However, in AA-genotypes carrier of VDR gene hypertensive women increased a risk of EH almost 3 times [OR = 3.08; 95% CI: 1.02–10.25; p = 0.047]. Conclusions: Thus, the mutant genotypes combinations of AGT (T704C) and VDR (1056T/C) genes don’t influence the risk of EH in population. However, AA-genotype of VDR gene in hypertensive women elevated risk of EH 3 times.

INTERCONNECTION BETWEEN TUBULAR RENAL DYSFUNCTION AND GENES POLYMORPHISM IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: Objective: to assess the relationship between NGAL concentration as an indicator of tubular disorders, and genetic markers of cardiovascular risk in hypertensive patients. Design and method: Materials and methods: 89 patients of working age with hypertension (mean age 48.32 ± 8.71) were examined, who were divided into 2 groups depending on serum NGAL. Group 1 - 20 patients with NGAL levels above reference values, Group 2 - 69 patients with NGAL levels in the range of normal values. For all patients, to evaluate tubular renal function, the concentration of NGAL in serum was determined by ELISA. All patients were examined for genotypes of AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met, ApoE Cys130Arg, PRARA rs4253778. Results: Results: patients in the groups did not significantly differ in age, gender, risk factors, concomitant diseases and therapy, blood pressure and lipid profile. In group 1, the occurrence of AGT, MTHFR, and PRARA gene polymorphism was significantly higher in heterozygous form than in group 2 (p = 0.002, p < 0.001, and p = 0.037, respectively). Patients in the groups did not significantly differ in occurrence of GNB3, MTRR, and ApoE gene polymorphism. Correlation analysis showed a direct relationship between the concentration of NGAL in the blood and the presence of AGT gene polymorphism (r = 0.38; p < 0.05), GNB3 (r = 0.33; p < 0.05), MTHFR (r = 0.35; p < 0.05). The association of NGAL with the polymorphism of the GNB3, MTRR, and ApoE genes was not statistically significant. Conclusions: Conclusions: in patients of working age with hypertension, tubular dysfunction, assessed by the concentration of NGAL in the blood, is associated with the presence of AGT, MTHFR, PRARA gene polymorphism in a heterozygous form.

ASSOCIATION OF AGT GENE M235T AND ACE GENE I/D POLYMORPHISMS WITH HYPERTENSION IN MONGOLIAN POPULATION

Objective: In Mongolia, hypertension is major public health problem due to its high prevalence of stroke and mortality rate. The objective of this study was to analyse the relationship between AGT M235T gene variant and ACE I/D gene variant with hypertension in a sample of the Mongolian population of the Ulaanbaatar city. Design and method: Design and Method: A case-control study has been performed in 146 subjects including 96 hypertensives and 50 normo-tensive subjects, aged 18–60 years. Hypertension was defined as systolic BP =>130 mm Hg and/or diastolic BP=>80 mm Hg). After isolation DNA from peripheral blood, the following specific primers were used for polymerize chain reaction (PCR). PCR purification kit and QIAquick Gel extraction kit were used to establish nucleic acid sequence. Results: The mean age of the participants was 39.6 years and 54.7% were men. The M235T variant of AGT gene was identified in 97.9% of all participants (96.8% of hypertensive patients and 100% of normotensive subjects). According to the genotype results, the frequencies of the AGT TT, MT and MM genotypes were 57.3%, 39.6%, and 3.1% in cases and 64.0%, 36.0% and 0.0% in controls respectively. The genotypic distribution of the M235T variant of the AGT gene did not differ in hypertensives and normotensives group (p > 0.328). In this study, we did not observe any significant differences in blood pressure levels with regard to ACE gene I/D polymorphism in both hypertensive and normotensive groups (40% vs 38%, p > 0.543). Conclusions: Conclusion: This is the first report on the frequency of AGT and ACE gene polymorphisms among Mongolian population. About 97.9% of Mongolians carry the M235T variant of the AGT gene that makes them more prone to hypertension when they eat too much sodium.

AGT, ACE, AGTR1, UMOD AND ADIPOQ GENES POLYMORPHISMS INTERACTIONS IN PREHYPERTENSION

Abstract Objective: Prehypertension (PHT) is recognized as a cardio-renal risk factor, and associated with progression to hypertension (HT). Studies of the genetic background of PHT have not been fully elucidated and the results suggested a possible role of genes involved in the etiopathogenesis of HT. The lack of data has prompted this study to hypothesize that hypertension and metabolic syndrome-related AGT rs2004776, ACE rs1799752, AGTR1 rs5186, UMOD rs13333226, ADIPOQ rs266729 and rs17300539 gene polymorphisms are more commonly found in subjects with PHT, than in subjects with optimal and normal blood pressure (BP). Design and method: A total of 601 subjects were included in this cross-sectional, observational study; 319 with high normal BP (PHT, 120–139/80–89 mmHg), ages 20–45, and 282 individuals with normal and optimal BP as a control group (NT). Results: The results indicated that the AGT, ACE, AGTR1, UMOD, and ADIPOQ gene polymorphisms were not found more frequently in PHT subjects than in NT. A significant difference was found in the number of rs266729 ADIPOQ heterozygous carriers; there were less carriers in the PHT group (35.1%) than in the NT group (44.7%), P < 0.03. The significance of the heterozygous model (CG vs GG/CC) of rs266729 ADIPOQ polymorphism in PHT in terms of reduced risk was observed (OR 0.66; 95% CI 0.47–0.92; P = 0.01). PHT was significantly associated with following haplotypes: hIAGCA ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729:AGTR1 (OR 1.56; 95%CI 1.08–2.24; P = 0.02), hIAGC ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.45; 95%CI 1.07–1.96; P = 0.02), hIAG ACE:UMOD:ADIPOQ_rs17300539 (OR 1.30; 95%CI 1.00–1.68; P = 0.05), hAGC UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.37; 95%CI 1.07–1.77; P = 0.01) and hAG UMOD:ADIPOQ_rs17300539 (OR 1.42; 95%CI 1.07–1.90; P = 0.02). Results emphasized two significant models of gene-gene-other determinants interactions with PHT, one model included creatinine, total cholesterol, alpha-1-microglobulin, ADIPOQ rs17300539 and UMOD rs13333228; and the second model includes ADIPOQ rs17300539, AGT rs2004776, cardiovascular risk, sex, BMI, and the gene-gene interaction AGTR1:ADIPOQ_rs266729:UMOD:ACE. Conclusions: The finding of five significantly related gene-gene interactions, as well as the discovery of their haplotypes that increase the PHT risk, and the finding of two gene-gene-other determinants interactions models, confirmed the good selection of genes, particularly UMOD and ADIPOQ, involved in various biological pathways responsible for controlling BP.

Molecular genetic diagnosis of hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic condition currently subdivided into two groups: HAE due to C1-inhibitor deficiency (Type I) or dysfunction (Type II) (C1-INH-HAE) and HAE with normal activity of C1‐INH (nC1- INH-HAE). C1-INH-HAE is estimated to occur in approximately 99 % of cases HAE and is caused by sequence variants in the SERPING1 gene. The prevalence of nC1-INH-HAE is extremely low and accounts for about 1 % of all cases of HAE. nC1-INH-HAE currently subdivided on HAE, due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 gene (KNG1-HAE), or angioedema of unknown origin (U-HAE).The amplicons of the entire coding regions and splice-sites of 18 genes from 24 patients (18 female) belonging to 17 families were analyzed by Next Generation Sequencing (NGS). The median age of patients was 33.5, of onset ‒ 16 years. 15 patients had a family history of edema.We identified seven C1-INH-HAE patients and variants were detected in the SERPING1 gene. For three patients (members of the same family), a heterozygous variant was found deep in the intron of the SERPING1 gene, which is likely to affect protein synthesis. We identified two patients with changes in the PLAUR gene, which may be associated with the manifestation of symptoms angioedema. Six patients showed abnormalities in the genes AGT and KNG1, which can probably explain their early hypertension, which could provoke the appearance of edema.

Polymorphism of genes of arterial hypertension among children with obesity and arterial hypertension

Arterial hypertension (АH) among obese children and adolescents is diagnosed with a frequency of 24,8 — 40 % of cases. The pathogenesis high blood pressure (HB) among childhood obesity continues to be studied in connection with the identification of new genetic and epigenetic factors that determine its course. Polymorphism of genes of arterial hypertension can serve as a reason for maintaining increased vascular tone, even if the nutritional status of the child is optimized. The objective was to study polymorphisms of genes of arterial hypertension AGT: 704, AGТ: 521; AGTR2: 1675; еNOS3:786 among children with obesity and arterial hypertension, depending from the dynamics of blood pressure after courses of diet and physical rehabilitation. Materials and methods. The study has included 50 obese and hypertensive children aged 11—14 years who were prescribed diet and courses of special physical exercises for 6 months. We have compared 2 groups of children: children who have had arterial hypertension after treatment («АH6 month +») and children who had no arterial hypertension after treatment («АH6 month -»). The comparison group has consisted of 34 healthy children with normal body mass index and blood pressure. We have performed clinical and instrumental, laboratory examination, anamnestic assessment of heredity, laboratory analysis of genotypic variants AGT: 704, AGТ: 521; AGTR2: 1675; еNOS3:786 among the studied population of children. Results. Comparative analysis of genotypic variants has showed a disproportionate distribution of alleles depending on the dynamics of blood pressure. Among children o «АH 6 month +» there were a predominance of mutant homozygous alleles of the gene AGTR2 AA (A) 45 % (22 %) and a decrease in the frequency a normal homozygous allele GG 9,0 % (9,6 %). We found a greater affinity of the CC homozygote for AGT 704, the CT heterozygote for AGT521 and the CC homozygote for the eNOS gene for the group of children «АH 6 month +» than among children «AH 6 months -» and healthy children. Conclusion. The revealing of causal polymorphisms of genes of arterial hypertension in obese children will allow predicting the risk of developing stable hypertension and determining treatment.