angiotensinogen and Essential-Hypertension

Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility.

Topics: Angiotensinogen; Essential Hypertension; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Hypertension; Polymorphism, Single Nucleotide; Risk Factors

The A-20C polymorphism in the angiotensinogen (AGT) gene has been associated with increased risk of essential hypertension in several studies; however, these studies gave inconsistent results. In this study, we performed a meta-analysis to assess the association between AGT A-20C polymorphism and essential hypertension. Published literature was retrieved from PubMed. Pooled odd's ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effect models. A total of 10 case-control studies containing 3653 cases and 3457 controls were enrolled to this meta-analysis. In a combined analysis, the results showed a significant association between the AGT A-20C polymorphism and risk of essential hypertension (AA vs CC: OR = 0.62, 95%CI = 0.46-0.84; recessive model: OR = 0.66, 95%CI = 0.49-0.88). In the subgroup analysis stratified by race, significant associations were found between the AGT A-20C polymorphism and essential hypertension risk in Asians (AA vs CC: OR = 0.59, 95%CI = 0.43-0.80; recessive model: OR = 0.63, 95%CI = 0.46-0.85). In conclusion, the results of this meta-analysis suggested that the AGT A-20C polymorphism was associated with risk of essential hypertension in Asians.

Topics: Angiotensinogen; Asian People; Essential Hypertension; Genetic Predisposition to Disease; Humans; Hypertension; Odds Ratio; Polymorphism, Single Nucleotide

The polymorphic angiotensinogen (AGT) gene is one of the most promising candidates for essential hypertension. The aim of this study was to examine the association between the A-6G variant of the AGT gene and the blood pressure response to angiotensin-converting enzyme (ACE) inhibitors in hypertensive subjects.. Five hundred and nine mildly to moderately hypertensive subjects received ACE inhibitors for six weeks after a two-week run-in period. AGT genotyping was performed by direct polymerase chain reaction amplification and deoxyribonucleic acid (DNA) nucleotide sequencing from peripheral blood.. The AA genotype, AG genotype, and GG genotype were present in 301 (59.1%), 186 (36.6%), and 22 (4.3%) of patients, respectively. As compared with patients carrying the AA or AG genotype, those carrying the GG genotype had significantly greater reductions in systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure (p=0.007, 0.014, 0.027 and 0.005, respectively). Moreover, stepwise multiple linear regression analysis showed that the A-6G genotype was a significant predictor of systolic blood pressure and pulse pressure reductions (p=0.040 and 0.019, respectively).. Our study indicates that the A-6G variant of the AGT gene may be an important determinant of interindividual variation in the response to ACE inhibitors.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Blood Pressure; Diastole; Essential Hypertension; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Hypertension; Male; Middle Aged; Promoter Regions, Genetic; Systole

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.

Topics: Aged; Alleles; Altitude; Angiotensinogen; Case-Control Studies; Essential Hypertension; Female; Genetic Predisposition to Disease; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Middle Aged; Models, Genetic; Polymorphism, Single Nucleotide; Tibet

To assess the synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs in Xinjiang.. A cross-sectional case-control association study was conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity on eight common single nucleotide polymorphisms (SNPs) interspersed over five genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Interactions among the SNPs were analyzed by the multifactor dimensionality reduction method (MDR).. In single-locus analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR: 0.683; 2.025). Interaction analysis by MDR showed that there was a strong synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction between both ACE I/D and CY11B2 T-344C and AGT A-6G.. There was a strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 -344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D were associated with male and female EH, respectively. H1 and H3 of AGT were protective and risk haplotypes, respectively.

Topics: Adult; Alleles; Angiotensinogen; Blood Pressure; China; Cross-Sectional Studies; Cytochrome P-450 CYP11B2; Essential Hypertension; Ethnicity; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide; Protective Factors; Renin-Angiotensin System

AGT is the first gene to be linked to essential hypertension (EHT). It harbors several variants of which only few polymorphisms are found to exhibit positive and negative associations with hypertension. In the present study, the AGT gene was screened to detect already reported and novel variations contributing to the development of hypertension.. In total, 215 hypertensives and 230 normotensives were screened for variations in all the five exons and a part of promoter of AGT gene using single strand conformation polymorphism analysis followed by sequencing of samples showing mobility shifts on polyacrylamide gels.. Five novel variants, namely c.-61G>A in promoter, c.-4+17C>T in intron1, c.24T>C and c.28A>T in Exon2, and c.*90 T>C in 3' untranslated region were detected in the AGT gene. c.-61G>A lies in the promoter region that plays a critical role in its expression. Variation c.-4+17C>T created a new enhancer site. c.24T>C (TCT-TCC) is a silent mutation while c.28A>T (p. M10L) has a possible damaging effect on the AGT protein. c.*90T>C, detected in the 3' untranslated region is thought to play an important role in the translation and stability of the mRNA.. Studies on the functional role of these novel variants are warranted to understand the mechanism underlying the development of EHT.

Topics: Alleles; Angiotensinogen; Essential Hypertension; Exons; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension; Polymorphism, Single Nucleotide; Promoter Regions, Genetic

Hypertension is a serious risk factor affecting up to 30% of the world's population with a heritability of more than 30-50%. The aim of this study was to investigate the contribution of the polymorphisms localized in the angiotensinogen (AGT) gene, a main component of the renin-angiotensin-aldosterone system, in inducing the susceptibility to essential hypertension (EH) among isolated populations (Yi and Hani minorities) with low prevalence rate from the remote region of Yunnan in China.. A case-control association study was performed, and all subjects were genotyped for the seven single nucleotide polymorphisms localized in the AGT region by polymerase chain reaction-restriction fragment length polymorphism analysis.. Three polymorphisms, i.e. rs5046, rs5049, and rs2478544, were significantly associated with EH among the Hani minority. The associations, found in the Yi minority, did not reach a conclusive level of statistical significance. The polymorphisms of rs2478544 and rs5046 caused the transformations of exonic splicing enhancer sites and transcription factor binding sites, respectively, in the bioinformatic analyses. The haplotype-rs5046T, rs5049A, rs11568020G, rs3789679C, rs2478544C was susceptible for EH among the Hani minority.. Our findings suggested that the AGT polymorphisms have played a vital role in determining an individual's susceptibility to EH among the isolated population, which would be helpful for EH management in the remote mountainous region of Yunnan in China.

Topics: Alleles; Angiotensinogen; Blood Pressure; Case-Control Studies; China; Computational Biology; Diastole; Essential Hypertension; Ethnicity; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Humans; Hypertension; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Risk Factors; Systole

Gene polymorphisms of the renin-angiotensin system are involved in the pathophysiology of hypertension. We genotyped 4 polymorphisms of angiotensinogen (AGT) gene A-20C (rs5050), A-6G (rs5051), C3889T (rs4762), and C4072T (rs699) by polymerase chain reaction-restriction fragment length polymorphism in 652 patients and 780 controls to examine the association of AGT and hypertension in a Northern Han Chinese population. There were significant differences in the distribution of genotypes and allele frequencies at C4072T between the patients and the controls (both P < .01); patients with CC genotype had a higher risk of hypertension (odds ratio = 1.7, 95% confidence interval 1.4-2.1). The distribution of genotypes at A-6G was significantly different between patients and controls (P < .05). No other significant differences in genotypes or frequencies were observed. No association was observed between the haplotypes of AGT and hypertension. The AGT-6A and 4072C alleles are associated with susceptibility to hypertension in this population.

Topics: Adult; Aged; Aged, 80 and over; Angiotensinogen; Asian People; Essential Hypertension; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Hypertension; Male; Middle Aged; Polymorphism, Genetic; Renin-Angiotensin System

Abstract Introduction: AGT gene harbors several variants of which 21 are found to be in high linkage disequilibrium as per Hapmap database. Studies delineating the importance of these tagged SNPs are very limited and lacking from Indian population. In the present study, we evaluated the contribution of four tagged SNPs namely, g.6635G > A, g.6506G > A, g.12840G > A, and g.13828T > C at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to essential hypertension (EHT).. About 215 hypertensives and 230 normotensives were genotyped for selected tagged SNPs using PCR-RFLP method.. Significant association was obtained for g.6635G > A and g.6506G > A polymorphisms wherein GG homozygotes for both the markers were at risk for developing the condition. g.13828T > C polymorphism specially, female heterozygotes (TC) were found to be at increased risk for EHT. Haplotype GGGC was found to have a significant protective effect (p = 0.0059). Markers g.6506G > A and g.12840G > A resulted in the creation of new enhancer sites thereby affecting splicing process.. The present report is the first one in the literature showing general- and gender-specific association of g.6506G > A and g.13828T > C polymorphisms, respectively, with EHT. However, further studies for replication of present observations are warranted from other populations and other parts of India.

Topics: Angiotensinogen; Case-Control Studies; Essential Hypertension; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Haplotypes; Humans; Hypertension; Linkage Disequilibrium; Male; Middle Aged; Models, Genetic; Polymorphism, Single Nucleotide; Risk Factors

The (pro)renin receptor ((P)RR) is expressed in several tissues including kidney, heart and brain, and is thought to regulate the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by furin to generate soluble (P)RR (s(P)RR), which is secreted into the extracellular space. s(P)RR is a candidate biomarker reflecting the status of the tissue RAS. Here, we investigated the relationship between background factors and serum s(P)RR levels. We measured s(P)RR levels in 122 patients with essential hypertension (EH) and assessed the relationships between background factors and s(P)RR levels. Serum s(P)RR levels were 19.0±4.9 ng ml(-1). Single regression analyses showed that age (r=0.251, P<0.01), serum creatinine levels (r=0.229, P<0.05) and urinary angiotensinogen excretion (r=0.196, P<0.05) were positively correlated with s(P)RR levels, whereas estimated glomerular filtration rate (eGFR; r=-0.337, P<0.001) were negatively correlated. Multiple regression analyses of age, blood pressure (BP), hemoglobin A1c (HbA1c) and s(P)RR levels revealed that age and s(P)RR levels were negatively correlated with the eGFR (P<0.05). In patients with EH, serum s(P)RR levels correlated positively with renal function independent of age, BP and HbA1c. These findings support s(P)RR as a useful biomarker that reflects the status of the tissue RAS.

Topics: Adult; Age Factors; Aged; Angiotensinogen; Essential Hypertension; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hypertension; Male; Middle Aged; Receptors, Cell Surface; Renin-Angiotensin System; Vacuolar Proton-Translocating ATPases