Angiotensinogen Variants among Resistant Hypertensive Patients.
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ABSTRACT:
SUBMITTER: Barbaro NR
PROVIDER: S-EPMC3982406 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Angiotensinogen Variants among Resistant Hypertensive Patients.
Barbaro Natalia Ruggeri NR Fontana Vanessa V Moreno Heitor H
International journal of hypertension 20140324
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Project description:We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II-dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels <30 mL/min per 1.73 m(2) were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139+/-3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151+/-4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122+/-2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio (r=0.5994), and urinary protein:creatinine ratio (r=0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00+/-4.96 microg/g) compared with normotensive subjects (13.70+/-2.33 microg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26+/-2.60 microg/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.
| S-EPMC2658771 | biostudies-literature
Project description:IntroductionThe plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population.MethodsNine polymorphisms in AGT gene were genotyped, and plasma AGT level was determined by enzyme-linked immunosorbent assay.ResultsDifferences in AGT plasma levels were associated with 2 polymorphisms: T-20G, TT = 25.3 ± 8.3 versus TG + GG = 21.6 ± 8.8 μg/mL; P = 0.008 and C3389T (T174M), CC = 25.8 ± 9.9 versus TC + TT = 20.5 ± 5.4 μg/mL; P = 0.0002. Haplotype 2 was associated with low plasma AGT (-5.1 μg/mL [95% confidence interval: -8.6 to -1.6], P = 0.004) and Haplotype 8 was associated with high plasma AGT (6.5 μg/mL [95% confidence interval: 2.5 to 10.6], P = 0.001). This association remained after adjustment for covariates. A Likelihood Ratio Test for haplotype-phenotype association adjusted for covariates resulted in χ = 38.9, P = 0.0005. The total effect of the haplotypes on plasma AGT level variance was 19.5%. No association was identified between haplotypes and quantitative traits of blood pressure.ConclusionsTwo polymorphisms (T-20G and C3389T) and 2 haplotypes (H2 and H8) showed an association with plasma AGT levels in Mexican population.
| S-EPMC3203016 | biostudies-literature
Project description:Despite a recent American Heart Association (AHA) consensus statement emphasizing the importance of resistant hypertension, the incidence and prognosis of this condition are largely unknown.This retrospective cohort study in 2 integrated health plans included patients with incident hypertension in whom treatment was begun between 2002 and 2006. Patients were followed up for the development of resistant hypertension based on AHA criteria of uncontrolled blood pressure despite use of ?3 antihypertensive medications, with data collected on prescription filling information and blood pressure measurement. We determined incident cardiovascular events (death or incident myocardial infarction, heart failure, stroke, or chronic kidney disease) in patients with and without resistant hypertension with adjustment for patient and clinical characteristics. Among 205 750 patients with incident hypertension, 1.9% developed resistant hypertension within a median of 1.5 years from initial treatment (0.7 cases per 100 person-years of follow-up). These patients were more often men, were older, and had higher rates of diabetes mellitus than nonresistant patients. Over 3.8 years of median follow-up, cardiovascular event rates were significantly higher in those with resistant hypertension (unadjusted 18.0% versus 13.5%, P<0.001). After adjustment for patient and clinical characteristics, resistant hypertension was associated with a higher risk of cardiovascular events (hazard ratio, 1.47; 95% confidence interval, 1.33-1.62).Among patients with incident hypertension in whom treatment was begun, 1 in 50 patients developed resistant hypertension. Patients with resistant hypertension had an increased risk of cardiovascular events, which supports the need for greater efforts toward improving hypertension outcomes in this population.
| S-EPMC3343635 | biostudies-literature
Project description:Corin is a serine protease that activates atrial natriuretic peptide (ANP). CORIN gene variants have been reported in patients with hypertension. To date, however, the prevalence of CORIN variants in hypertensive patients remains unknown. To understand the prevalence and functional significance of CORIN variants in hypertension, we sequenced CORIN exons in 300 normal and 401 hypertensive individuals in a Chinese population and identified nine nonsynonymous variants, of which eight were not characterized previously. Among them, variants c.131A > G (p.Tyr13Cys), c.376G > T (p.Asp95Tyr), c.1094T > G (p.Leu334Trp), and c.1667G > A (p.Arg525His) occurred similarly in both normal and hypertensive individuals. Variants c1139G > A (p.Arg349His), c.2689C > T (p.Pro866Ser), and c.2864C > T (p.Thr924Met) were found once each in hypertensive individuals. Variant c.1683G > T (p.Arg530Ser) occurred preferentially in hypertensive individuals [10/401 (2.5%) vs. 1/300 (0.3%) in normal individuals; P = 0.023], which was confirmed in another independent cohort [9/368 (2.44%) in hypertensive and 2/377 (0.53%) in normal individuals; P = 0.033]. In biochemical and cell-based functional studies, variants p.Arg530Ser and p.Thr924Met, but not p.Tyr13Cys, p.Asp95Tyr, p.Leu334Trp, p.Arg349His, p.Arg525His, and p.Pro866Ser, exhibited reduced pro-ANP processing activity, which was caused by endoplasmic reticulum retention and poor zymogen activation, respectively. These results indicate that genetic variants impairing corin function are not uncommon in general populations and that such variants may be an important contributing factor in hypertension.
| S-EPMC5794343 | biostudies-literature
Project description:BACKGROUND:Treatment resistant hypertension(TRH) is detrimental risk of cardiovascular and premature deaths. Globally, the prevalence of resistant hypertension is inclining from time to time and it is yet to be determined in Ethiopia. OBJECTIVE:To assess the prevalence of apparent TRH and its predictors among ambulatory hypertensive patients on follow up in hypertension clinic of Mekelle Hospital, Northern Ethiopia. METHOD:A hospital based cross sectional study was conducted from Nov 25, 2018 to July 20, 2019, among 338 adult ambulatory hypertensive patients on follow up in Mekelle Hospital hypertension clinic. Hypertensive patient aged ≥18 years who were on regular follow up and taking antihypertensive medications for at least 6 months were included in the study. A simple random sampling technique was used to recruit the study patients. RESULTS:A total of 338 adult ambulatory hypertensive patients were analysed. More than half, 182 (53.8%) patients were females and the average age of the patients was 58.9 ±11.5. Three hundred thirty-three (98.5%) patients had no family history of hypertension. Majority, 66.8% of the patients were on monotherapy. The prevalence of apparent TRH was calculated to be 8.6% [Confidence Interval = 0.056-0.116]. Patients with Body Mass Index(BMI) greater than 30[Adjusted Odds Ratio(AOR) = 12.1, 95%CI:2.00-73.19, p = 0.007] and longer duration of hypertension were the predictors of resistant hypertension. CONCLUSION:Even if escalation of antihypertensive medications was not aggressive, apparent TRH was common in the study setting. Obesity (BMI greater than 30) and longer duration of hypertension since diagnosis were the predictors of TRH. Meticulous emphasis should be placed on to detect the prevalence of true hypertension resistance and future studies should discover the impact of aggressive antihypertensive medications scale up on the risks of TRH.
| S-EPMC7188288 | biostudies-literature
Project description: Not available
| S-EPMC4038250 | biostudies-literature
Project description:BackgroundThe renin-angiotensin system (RAS) plays an important role in regulating blood pressure and controlling sodium levels in the blood. Hyperactivity of this system has been linked to numerous conditions including hypertension, kidney disease, and congestive heart failure. Three classes of drugs have been developed to inhibit RAS. In this study, we provide a structure-based analysis of the effect of single nucleotide variants (SNVs) on the interaction between renin and angiotensinogen with the aim of revealing important residues and potentially damaging variants for further inhibitor design purposes.ObjectivesTo identify SNVs that have functional and potentially damaging effects on the renin-angiotensinogen complex and to use computational approaches to investigate how SNVs might have damaging effects.MethodsA comprehensive set of all known SNVs in the renin and angiotensinogen proteins was extracted from the HUMA database. This dataset was filtered by removing synonymous and missense variants and using the VAPOR pipeline to predict which variants were likely to be deleterious. Variants in the filtered dataset were modeled into the renin-angiotensinogen complex using MODELLER and subjected to molecular dynamics simulations using GROMACS. The residue interaction networks of the resultant trajectories were analyzed using graph theory.ConclusionsThis research identified important SNVs in the interface of RAS and showed how they might affect the function of the proteins. For instance, the mutant complex containing the variant P40L in angiotensinogen caused instability in the complex, indicating that this mutation plays an important role in disrupting the interaction between renin and angiotensinogen. The mutant complex containing the SNV A188V in renin was shown to have significantly increased fluctuation in the residue interaction networks. D104N in renin, associated with renal tubular dysgenesis, caused increased rigidity in the protein complex comparison to the wild type, which probably in turn negatively affects the function of RAS.
| S-EPMC5583000 | biostudies-literature
Project description:Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.
| S-EPMC4670722 | biostudies-literature
Project description:PurposeTo evaluate (i) the outcome of swallowing therapy program on the rehabilitation of oropharyngeal dysphagia in resistant hypertensive patients with obstructive sleep apnea (OSA) and (ii) the association between the clinical and anthropometric characteristics of these individuals and this outcome.MethodsThis was a prospective interventional study in which resistant hypertensives diagnosed with OSA by polysomnography and dysphagia by fiberoptic endoscopic evaluation of swallowing (FESS) participated. All participants underwent a FEES and assessment of the risk of dysphagia (Eating Assessment Tool, EAT-10) and swallowing-related quality of life (Swal-QoL) before and after the intervention. The therapeutic program was performed daily by the participants, with weekly speech-therapist supervision for eight weeks, including the following strategies: Masako, chin tuck against resistance, and expiratory muscle training.ResultsA total of 26 (78.8%) of the participants exhibited improvement in the degree of dysphagia in the intervention outcome. After the intervention, there was a statistically significant improvement in the level of penetration-aspiration (p = 0.007), the degree of pharyngeal residue (p = 0.001), the site of onset of the pharyngeal phase (p = 0.001), and the severity of dysphagia (p = 0.001) compared to before intervention. The EAT-10 score was 2 (0-6) before and 0 (0-3) after intervention (p = 0.023). Swal-QoL had a score on the symptom frequency domain of 92.8 (75-100) before and 98.2 (87.5-100) after intervention (p = 0.002).ConclusionsResistant hypertensive patients with OSA showed improved swallowing performance after swallowing therapy program.
| S-EPMC9469056 | biostudies-literature
Project description:Introduction:This study aimed to investigate whether mononucleotide polymorphisms of the angiotensinogen gene at promoter were associated with the blood-pressure-lowering response to telmisartan treatment.Materials and methods:After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy with 80 mg/day of telmisartan and then were followed up for eight weeks. The -6A/G and -20A/C polymorphisms of the angiotensinogen gene at promoter were determined through polymerase chain reaction and restriction fragment length polymorphsim analysis. The relationship between these polymorphisms and changes in blood pressure was observed and evaluated after eight weeks of treatment.Results:There were no significant differences between -6A/G, -20A/C polymorphisms of the angiotensinogen gene and blood pressure reductions after treatment, p>0.05.Conclusion:It is suggested that angiotensinogen-6 A/G and angiotensinogen-20 A/C polymorphisms were not associated with the antihypertensive response to telmisartan treatment in Chinese patients with hypertension.
| S-EPMC6362516 | biostudies-literature