Aldosterone Synthase Gene Polymorphism Research Articles

Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan.

Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the Pakistani community prompted us to design this study. Aldosterone synthase (CYP11B2) was thoroughly studied in different ethnic groups; however, no such study has been conducted in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. In essential hypertension, the aldosterone synthase gene (CYP11B2) plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the CYP11B2 gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase (CYP11B2) gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between CYP11B2 gene polymorphism and hypertension in Pakistan's Pashtun population. We used the nascent exome sequencing method to identify variants associated with hypertension. The research was divided into two phases. In phase one, DNA samples from 200 adult hypertension patients (of age ≥ 30 years) and 200 controls were pooled (n = 200/pool) and subjected to Exome Sequencing. In the second phase, the WES reported SNPs were genotyped using the Mass ARRAY technique to verify and confirm the association between WES-identified SNPs and hypertension. WES identified a total of eight genetic variants in the CYP11B2 gene. The chi-square test and logistic regression analysis were used to estimate the minor allele frequencies (MAFs) and chosen SNPs relationships with hypertension. The frequency of minor allele T was found to be higher in cases compared to the control (42% vs. 30%: p = 0.001) for rs1799998 of CYP11B2 gene, while no significant results (p > 0.05) were observed for the remaining SNPs; rs4536, rs4537, rs4545, rs4543, rs4539, rs4546 and rs6418 showed no positive association with HTN in the studied population (all p > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan.

Альдостеронсинтаза, поліморфізм її гена CYP11B2 при артеріальній гіпертензії і асоційованих з нею кардіоваскулярних захворюваннях (огляд літератури)

В огляді надані дані зарубіжної та вітчизняної літератури щодо патогенетичної ролі альдостерону, рівнів альдостеронсинтази і поліморфізмів гена даного ферменту у хворих на різні форми артеріальної гіпертензії, при асоційованих з нею захворюваннях серця і судин, фібриляції передсердь, метаболічному синдромі, патології нирок, головного мозку. Розглядаються функції альдостерону, рівнів альдостеронсинтази і поліморфізмів гена даного ферменту в серцево-судинному ремоделюванні, можливості застосування даних маркерів для диференційно-діагностичних цілей, перспективи терапевтичного використання інгібіторів альдостеронсинтази серед різних категорій хворих з ознаками артеріальної гіпертензії.

Contribution of the ACE (rs1799752) and CYP11B2 (rs1799998) Gene Polymorphisms to Atrial Fibrillation in the Tunisian Population.

This study investigated the association of angiotensin-converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants (p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39-8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48-21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62-8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22-5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08-11.77]; p < 0.03). Furthermore, the haplotype-based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population.

Associations of excess myocardial mass, echoreflectiveness and aldosterone synthase gene polymorphism in men with hypertension

Hypertensive remodeling of the left ventricle (LV) is largely due to the influence of a number of control genes. In particular, the regulatory gene CYP11B2, which is responsible for the activity of aldosterone in blood plasma, affects the processes of cardiomyocyte hypertrophy, myocardial fibrosis and microcirculation. This study is devoted to the search for the effect of polymorphic aldosterone synthase carriers on the severity of the components of left ventricular hypertrophy in men with essential hypertension (EH) and representatives of the control group, residents of Podyllia region. The aim of the study was to determine associations between excess (inappropriate) myocardial mass, parameters of standard echocardiography and parameters of echoreflectivity in men with essential hypertension, carriers of different polymorphic variants of aldosteronesynthase gene. The study involved 150 men, aged 45-60 years, residents of the Podyllia region, who had no irreversible damage of target organs. Among them, 50 were in the control group, 58 – had EH of 1st stage and 42 men had EH of 2nd stage. All participants were measured for office blood pressure, performed a standard echocardiographic examination with the addition of standard EchoCG protocol by determination of the parameters of echoreflectivity and evaluation of appropriateness of left ventricular l mass (LVM) to hemodynamic load, according to the formula de Simone et al. and calculating the excessiveness ratio (ER) and determined the C-344T polymorphism of the CYP11B2 gene in venous blood samples by PCR. Statistical processing of the obtained results is performed using a specialized statistical application “Statistica 12.0”. It was found that the prevalence of CC polymorphism of the CYP11B2 gene in men with inappropriate LVM was almost twice higher than in men with appropriate to hemodynamic load LVM (p=0.015 by criterion χ2). At the same time, men with inappropriate LVM were characterized by higher values of echoreflectivity parameters BB and mCSV. In contrast to patients of the control group and patients with EH of 1st stage, patients with EH of 2nd stage, actual LVM (287.4 (53.9) g) significantly (p&lt;0.001) exceeded the predicted values (189 (37.8) g). According to the results of Spearman's rank correlation analysis, it was found that the carrier of the CC genotype of aldosterone synthase gene is associated with higher values of the LVM ER. Thus, patients carrying the polymorphic CC variant of CYP11B2 gene are characterized by more pronounced cardiomyocyte hypertrophy, greater excess of LV mass relative to individual hemodynamic needs, more aggressive processes of myocardial fibrosis.

Pharmacogenetic study of ACE, AGT, CYP11B1, CYP11B2 and eNOS gene variants in hypertensive patients from Faisalabad, Pakistan.

To investigate the association of genetic variants of renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes, and the drug efficacy of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. This two time-point study was conducted from April to November 2016 at Allied Hospital, Faisalabad and National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, and comprised of hypertensive patients taking angiotensin-converting enzyme inhibitor and angiotensin receptor blocker who were followed up for 12 weeks. Baseline and follow-up clinical and biochemical parameters were measured for all patients. Total 11 polymorphisms were genotyped by polymerase chain reaction, polymerase chain reaction-restriction fragment length polymorphism and amplification-refractory mutation system-polymerase chain reaction assays. Data was divided into baseline and follow-up groups, while the latter group was further divided into responding and non-responding subgroups on the basis of patient response to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker drugs. Data was analysed using SPSS 20. Of the 45 patients, 25(55.5%) were females and 20(44.5%) were males. There was a significant reduction in the systolic blood pressure (p=0.004) and low-density lipoprotein cholesterol (p<0.001) from the baseline to the follow-up. Systolic blood pressure was significantly reduced in the responding group (p=0.003), while diastolic blood pressure (p=0.121) was not significantly different. There was no effect of angiotensin-converting enzyme, angiotensinogen, 11-beta-hydroxylase, aldosterone synthase and endothelial nitric oxide synthase gene polymorphisms on angiotensin converting enzyme inhibitor and angiotensin receptor blocker efficacy. Inter-individual response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker was found to be independent of genetic polymorphisms in renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes.

Associations of aldosterone synthase gene polymorphism and atrial fibrillation affected by coronary heart disease in elderly and senile patients

Given the significant increase in the frequency of atrial fibrillation (AF) in elderly and senile patients with confirmed coronary heart disease (CHD), the study of the relationship between the polymorphisms responsible for the functioning of the renin-angiotensinaldosterone system and the presence of this disease becomes relevant. Purpose of the study. To study the genetic polymorphism of the CYP11B2 gene in elderly patients with ischemic heart disease, as well as to identify the role of aldosterone synthetase in the development of AF in this category of patients. Materials and methods. The study included 140 patients of both sexes (54,3% – men), over the age of 60 years, with confirmed coronary artery disease and any form of AF (the last episode no later than 12 months from the date of inclusion in the study). 84 patients agreed to participate in the study of aldosterone synthase polymorphisms. The control group consisted of 34 patients who had no diagnosed non-infectious diseases at the time of the survey. Both groups were comparable in age and sex characteristics. Results. Comparative evaluation of the distribution of genotypes and alleles – C344/T of the aldosterone synthase gene among patients with AF+CHD and relatively healthy individuals revealed that in the first group, most patients had the CYP11B2 T/T genotype in 38,1% of cases, the incidence was higher, than in patients of the comparison group – 14,7% (OR = 3.44, CI 1.07-11.07, p = 0.038). The frequency of detection of genotypes of CYP11B2 С/T and CYP11B2 С/С did not significantly differ in the compared groups. In the group with AF+CHD, the T allele was significantly more common (53,6% vs. 35,3%; p&lt;0,05), while the frequency of occurrence of allele C was significantly higher in the group of relatively healthy individuals (64,3% vs. 47,1%; p&lt;0,05). Conclusion. AF in elderly and senile patients with CHD is associated with the presence of CYP11B2 T/T genotype (OR = 3,44, DI 1,07–11,07, p = 0,038) and is not associated with myocardial echocardiographic parameters, including the size of left atrium.

Significance of aldosterone synthase gene (CYP11B2) polymorphism as a component of the renin-angiotensin-aldosterone system in the pathogenesis of myocardial hypertrophy in hypertension: literature review and own experience

Aldosterone synthase gene is one of the candidate genes responsible for the effects of aldosterone. In particular, there are some evidences concerning the influence of this gene on the myocardial remodeling in hypertension. The analysis and summary of the results of published researches devoted to the study of aldosterone synthase gene (CYP11B2) polymorphism and its importance in the processes of hypertensive myocardial remodeling are presented in the article. Pub Med and EMBASE databases were used. The results of the study of CYP11B2 polymorphism within the framework of the research work at the Department of Internal Medicine of Medical Faculty №2 are presented in the article. The aim of the study is to study the importance of polymorphism of aldosterone synthase gene in the pathogenesis and clinic of hypertension. It has been shown that among both, hypertensive and males, residents of Podillia region of Ukraine, the overwhelming majority were carriers of TC polymorphism of CYP11B2 gene. These data are in the agreement with the previous studies in the European population.

Genetic aspects of primary hyperaldosteronism.

Primary hyperaldosteronism (PHA) is the most common form of secondary hypertension of hormonal origin. It affects about 10% of all hypertensive patients. It is connected with increased morbidity and mortality from cardiovascular diseases (CVD) compared to patients with essential hypertension of a similar age. Usually, it is an effect of bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenoma (APA), more rare causes of PHA are: unilateral adrenal hyperplasia, aldosterone-producing adrenocortical carcinoma, ectopic aldosterone-producing tumors and familial hyperaldosteronism. Recent genetic studies have thrown a new light on the pathogenesis of PHA, classifying it as a channelopathy. Several mutations within the ion channels encoding genes have been identified. A possible link between primary hyperaldosteronism and polymorphism of aldosterone synthase gene and ion channel genes is still being investigated. In this manuscript, we focus on genetic aspects of primary hyperaldosteronism, and present an up-to-date compilation of available data with the widened pathogenetic approach.

The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients.

Longevity of peritoneal membrane is an important issue in patients treated with peritoneal dialysis (PD). In our study, we studied the impact of angiotensin receptor 1 (AGT R1) and aldosterone synthase (CYP11B2) gene polymorphism on peritoneal concentrations of interleukin-6 (PI-IL-6), vascular endothelial growth factor (PI-VEGF), plasminogen activator inhibitor-1 (PI-PAI-1), transforming growth factor-β (PI-TGF-β), and cancer antigen-125 (PI-CA-125) as known markers of peritoneal fibrosis. The single nucleotide polymorphism rs5186 (A1166C) in AGT R1 gene is located in 3' untranslated region (UTR) of the gene, while polymorphism rs1799998 (T -344 C) in CYP11B2 gene is located in the promoter region of the gene. We compared marker concentrations in patients with genotype DD vs. Dd and dd for AGT R1 and patients with genotype HH vs. Hh and hh for CYP11B2. The results show that polymorphism of CYP11B2 gene is associated with serum concentration of aldosterone. Patients with genotype HH had statistically significantly lower serum concentration of aldosterone (p=0.04). These patients also showed a trend to a lower rate of production of I-IL-6 (p=0.07), which correlated with lower concentrations of PAI-1 (p=0.002) and VEGF (p=0.005). AGT R1 gene polymorphism did not show any association with studied variables. Our findings suggest the possibility of genetic predisposition for development of peritoneal fibrosis that could be important for identification of patients with an "unfavorable" genotype, which could lead to customized prescription of appropriate therapy and personalized patient management. .

Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD) and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544) were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

Gene polymorphism of aldosterone synthetase (CYP11B2) variants and main cardiovascular risk factors

Background. Purpose of the work – to investigate the possible relationship of the cardiovascular risk main factors with certain polymorphism of aldosterone synthase gene (CYP11B2).Materials and methods. Аt the Cardiology Department of PL Shupyk NMAPE general clinical examination of 378 patients was held. Patients were divided into four groups: 100 patients with postinfarction cardiosclerosis, 78 patients with CAD without myocardial infarction in history, 100 high cardiovascular risk patients (with diabetes, hypertension or dyslipidemia) and 100 healthy patients (absence of cardiovascular disease was confirmed by medical history, ECG, blood pressure measurement and stress-ECG).Genetic testing was performed by polymerase chain reaction in real time at the Institute of Physiology named after O. O. Bogomolets.Exclusion criteria were hemodynamically significant valvular heart disease, chronic obstructive pulmonary disease, permanent or temporary heart pacing, acute heart failure and implanted cardioverter-defibrillator, permanent form of atrial fibrillation.Statistical analysis of the results was performed using Microsoft Excel, the statistical program SPSS (version 13US).Results. When analyzing the average levels of low density lipoprotein (LDL) cholesterol statistically significant difference between the group of patients with postinfarction cardiosclerosis and the group of high-risk patients (2.93±1.2 mmol/L vs 3.4±1.2 mmol/L, p=0.0075) was demonstrated, indicating a better cholesterol control in the group of patients with postinfarction cardiosclerosis, despite the fact that the average cholesterol level did not reach the target.The highest average levels of triglycerides (TG) were observed in patients with postinfarction cardiosclerosis – 1.56±0.725 mmol/L, intermediate – in patients with stable coronary artery disease – 1.39±0.795 mmol/L, and the lowest – in high cardiovascular risk patients – 1.04±0.565 mmol/L, with significant differences between all groups. The level of total cholesterol in patients with postinfarction cardiosclerosis was significantly higher in the subgroup of patients with homozygous recessive variant CC (5.8±1.08 mmol/L), compared with heterozygotes TC (4.87±1.3 mmol/L, p=0.024 ) and had no statistical significance when compared with the dominant TT homozygotes (5.06±1.45 mmol). Higher levels of total cholesterol (5.76±1.5 mmol/L) in TT homozygotes compared with TC (4.92±1.27 mmol/L, p=0.027) and CC (4.74±1.23 mmol/L, p=0.022) were found. In the group of patients with postinfarction cardiosclerosis, LDL cholesterol in the subgroup homozygous recessive variant CC was higher (3.43±0.87 mmol/L) (not significant) compared with a TT variant (3.02±1.3 mmol/L) and compared with heterozygotes TC (2.78±1.2 mmol/L, p=0.08). The level of TG in patients with stable coronary heart disease was the lowest in dominant homozygotes TT (1.13±0.56 mmol/L) compared with CT heterozygotes (1.54±0.97 mmol/L, p=0.08) and CC homozygotes (1.36±0.58 mmol/L, p=0.2).Conclusions.1. Group of high cardiovascular risk patients requires special attention in the prevention of cardiovascular diseases, because this group showed the worst control of cardiovascular risk factors (level of total cholesterol, LDL cholesterol, glucose, SBP) in the absence of appropriate treatment.2. Ingroup of patients with stable coronary artery disease and postinfarction cardiosclerosis the link CC variant gene polymorphism of aldosterone synthase CYP11B2-344C/T with higher levels of total cholesterol, LDL cholesterol was established, which increases the cardio-vascular risk in this group.3. CC polymorphism of aldosterone synthase gene CYP11B2-344C/T was associated with higher levels of SBP in patients with stable coronary artery disease and postinfarction cardiosclerosis, which increases the cardiovascular risk such as the development of hypertension.

Haplotype association and synergistic effect of human aldosterone synthase (CYP11B2) gene polymorphisms causing susceptibility to essential hypertension in Indian patients

ABSTRACTBackground: Aldosterone synthase (CYP11B2) is a key enzyme involved in the terminal steps of aldosterone biosynthesis. Genetic variability in CYP11B2 gene has been associated with heterogeneous aldosterone production, which can affect sodium homeostasis and thereby regulation of blood pressure. Hence, the present study was aimed to explore the single-locus variations, haplotype and epistasis patterns of CYP11B2 (C-344T, intron-2 gene conversion and Lys173Arg) gene polymorphisms, and the risk contributed by them to the development of essential hypertension (EHT). Methods: A total of 279 hypertensive patients and 200 normotensive controls were enrolled in this study. C-344T and Lys173Arg polymorphisms of CYP11B2 gene were genotyped by PCR-RFLP method and intron-2 gene conversion (IC) polymorphism by allele-specific PCR analysis. Results: Single-locus analysis revealed significant association of CYP11B2 C-344T and Lys173Arg polymorphisms with EHT (p < 0.05). Considering the sexes, Lys173 allele was found to be at risk for hypertension in males (OR 1.40; 95% CI = 1.01–1.96). Unphased haplotype analysis revealed H1 (T-Conv-Lys; p = 0.0017) to have significant risk for EHT, while haplotype H4 (T-Wt-Arg) had a significant protective effect. Multifactor dimensionality reduction (MDR) interaction analysis found the overall best model with C-344T and IC polymorphisms exhibiting strong synergistic effect. Conclusion: The present study revealed a strong synergistic effect of CYP11B2 C-344T and IC polymorphisms causing susceptibility to EHT and haplotype H1 (-344T-Conv-Lys173) as the risk-conferring factor for hypertension predisposition.

Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis.

Introduction:Studies on the relation between aldosterone synthase -344 T/C polymorphism and diabetic nephropathy showed controversial conclusions. This meta-analysis aimed to systematically summarize the association between aldosterone synthase (CYP11B2) gene polymorphism and diabetic nephropathy risk.Methods:Embase, PubMed, ScienceDirect, Web of Science, Wanfang Data, VIP Database, China Knowledge Resource Integrated Database and SinoMed have been searched. A total of five studies including 825 cases and 910 controls were included.Results:In overall analysis, significant increased risk was found in recessive comparison (OR = 1.27, 95% CI 1.05–1.55), homozygote comparison (OR = 1.39, 95% CI 1.04–1.88) and allele comparison (OR = 1.20, 95% CI = 1.05–1.39). No significant association was detected in dominant comparison (OR = 1.27, 95% CI 0.97–1.66) and heterozygote comparison (OR = 1.17, 95% CI 0.88–1.56). In subgroup analysis, significant increased risk existed in Asian population in allele comparison (OR = 1.45, 95% CI = 1.17–1.79), dominant comparison (OR = 1.78, 95% CI 1.11–2.87), homozygote comparison (OR = 2.11, 95% CI 1.29–3.47), recessive comparison (OR = 1.54, 95% CI 1.17–2.03), except for heterozygote comparison (OR = 1.44, 95% CI 0.87–2.38).Conclusions:Our meta-analysis indicates that aldosterone synthase (CYP11B2) gene polymorphism may contribute to diabetic nephropathy development, especially in Asian group, with the T allele acting as a risk factor.

RETRACTED: Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy.

The following article has been included in a multiple retraction: Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System ( JRAAS) 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the JRAAS (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer-review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online-first articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314563426, first published 18 December 2014. DOI: 10.1177/1470320314563426 . Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy JRAAS 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . Weiqiang Zhong, Zongpei Jiang and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population JRAAS1470320314566019, first published 26 January 2015. DOI: 10.1177/1470320314566019 . Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population JRAAS 1470320314563425, first published 1 February 2015. DOI: 10.1177/1470320314563425 . Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314566221, first published 1 February 2015. DOI: 10.1177/1470320314566221 . Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression JRAAS 1470320314568521, first published 3 February 2015. DOI: 10.1177/1470320314568521 . Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population JRAAS March 2015; 16: 165-171, first published 14 November 2014. DOI: 10.1177/1470320314557849 . Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang and Tian-Biao Zhou Association of aldosterone synthase ( CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy JRAAS September 2015; 16: 660-665, first published 20 August 2014. DOI: 10.1177/1470320314524011 .

Human aldosterone synthase gene polymorphism promotes miRNA binding and regulates gene expression.

Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure. Like other complex diseases, hypertension is caused by a combination of genetic and environmental factors. The renin-angiotensin-aldosterone system plays an important role in the regulation of blood pressure. The octapeptide angiotensin II (ANG II) is one of the most active vasopressor agents and is obtained from the precursor molecule, angiotensinogen, by the combined proteolytic action of renin and angiotensin-converting enzyme. ANG II increases the expression of aldosterone synthase (coded by Cyp11B2 gene), which is the rate-limiting enzyme in the biosynthesis of aldosterone. Previous studies have shown that increased expression of aldosterone synthase increases blood pressure and cardiac hypertrophy in transgenic mice. Human Cyp11B2 gene has a T/C polymorphism at -344 positions in its 5'-untranslated region (UTR), and the -344T allele is associated with hypertension. Human Cyp11B2 gene also has an A/G polymorphism at 735 position in its 3'-UTR (rs28491316) that is in linkage disequilibrium with single nucleotide polymorphism at -344. We show here that 1) microRNA (miR)-766 binds to the 735G-allele and not the 735A-allele of the hCyp11B2 gene and 2) transfection of miR-766 reduces the human aldosterone synthase mRNA and protein level in human adrenocortical cells H295R. These studies suggest that miR-766 may downregulate the expression of human aldosterone synthase gene and reduce blood pressure in human subjects containing -344T allele.

RETRACTED: Association of aldosterone synthase (CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy

This meta-analysis was conducted to assess the association of aldosterone synthase (CYP11B2) gene polymorphism with the risk of immunoglobulin A (IgA) nephropathy (IgAN) and the progression of IgAN. The literature on associations was identified from PubMed and the Cochrane Library on 1 October 2013, and eligible reports were synthesized. Eligible reports were recruited into this meta-analysis for the association of CYP11B2-344C/T (rs1799998) gene polymorphism with IgAN risk, and the progression of IgAN. In this meta-analysis, the association of CYP11B2-344C/T (rs1799998) gene polymorphism with IgAN risk was not found in overall populations and in Asians. Interestingly, the C allele and CC genotype were associated with the risk of IgAN in Caucasians, but the TT genotype was not. CYP11B2-344C/T gene polymorphism is not associated with IgAN risk and IgAN progression in overall populations and in Asians, but CYP11B2 C allele and CC genotype were associated with the risk of IgAN in Caucasians. However, more studies should be performed in the future to confirm this association.

Aldosterone synthase gene polymorphism in patients with hypertension combined ischemic heart disease with in various left ventricular mass

Study purpose - assessment of the relationship of levels of aldosterone and natriuretic peptide plasma aldosterone synthase gene polymorphism variants in patients with coronary heart disease (CHD) in combination with arterial hypertension (AH) at different left ventricular mass.Materials and methods. The study involved 63 male with hypertension and CHD; there were 32 men with signs of left ventricular hypertrophy (LVH) and 31 men with coronary artery disease with hypertension with a normal index of left ventricular mass. Evaluated the concentrations of aldosterone and plasma natriuretic peptide (NUP) in the relationship with characteristic of aldosterone synthase gene polymorphism.Results. It is established that the genotype CYP11В2 T/С of is associated with increased levels of aldosterone and signs of left ventricular hypertrophy. The level of LVC in the signs of LVH group was 2,1 fold higher than in patients without LVH. For patients with evidence of left ventricular hypertrophy is characterized by: the genotype of CYP11В2 T/C (62,5% of cases), the identification of the T allele (1,3 times more likely than patients without evidence of LVH) and more rarely than with normal index of left ventricular mass occurs variant CYP11В2 T/Т and more rarely prevalent allele C. Conclusion. In patients with coronary artery disease and hypertension, it is reasonable to implement in practice population genetic analysis to assess the probability the formation of left ventricular hypertrophy in the early stages of the disease.

Полиморфизм гена альдостеронсинтазы у больных артериальной гипертензией в сочетании с ишемической болезнью сердца при различной массе миокарда левого желудочка

Study purpose - assessment of the relationship of levels of aldosterone and natriuretic peptide plasma aldosterone synthase gene polymorphism variants in patients with coronary heart disease (CHD) in combination with arterial hypertension (AH) at different left ventricular mass.Materials and methods. The study involved 63 male with hypertension and CHD; there were 32 men with signs of left ventricular hypertrophy (LVH) and 31 men with coronary artery disease with hypertension with a normal index of left ventricular mass. Evaluated the concentrations of aldosterone and plasma natriuretic peptide (NUP) in the relationship with characteristic of aldosterone synthase gene polymorphism.Results. It is established that the genotype CYP11В2 T/С of is associated with increased levels of aldosterone and signs of left ventricular hypertrophy. The level of LVC in the signs of LVH group was 2,1 fold higher than in patients without LVH. For patients with evidence of left ventricular hypertrophy is characterized by: the genotype of CYP11В2 T/C (62,5% of cases), the identification of the T allele (1,3 times more likely than patients without evidence of LVH) and more rarely than with normal index of left ventricular mass occurs variant CYP11В2 T/Т and more rarely prevalent allele C. Conclusion. In patients with coronary artery disease and hypertension, it is reasonable to implement in practice population genetic analysis to assess the probability the formation of left ventricular hypertrophy in the early stages of the disease.

Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor

Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients. Patients with kidney graft biopsy were divided according to the presence or absence of CIN. We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. Histological, biochemical and clinical variables were measured. Calcineurin inhibitor (CI) levels were significantly higher in patients with the int 2 WW genotype than in patients with WC or CC genotypes. There was a greater degree of interstitial fibrosis in patients with int 2 CC genotype. No relationship was found between the different polymorphisms and a higher degree and/or frequency of CIN. There was also no relationship with plasma aldosterone levels. The frequency of the different polymorphisms studied was not related to plasma aldosterone levels or the development of CIN; however, the int 2 CC genotype was related to a greater degree of interstitial fibrosis, whereas the WW genotype was related to higher CI serum levels.

Relations between large artery structure and function and aldosterone

Aldosterone influences independently the vascular environment in humans, acting through structural and functional modifications of the arterial wall as derived from mineralocorticoid receptors. In rats, aldosterone infusion increases arterial stiffness in the presence of high-sodium intake, together with development of extracellular matrix and inflammatory factors. A selective increase in systolic and pulse pressure ensues, causing predominant organ damage on the heart, kidney and large arteries. In humans at rest, but independently of mean arterial pressure, arterial stiffness and wave reflections are associated with a steeper increase in these parameters with age. This finding is observed mainly with the CC genotype and not the TT or the TC genotype of the aldosterone synthase gene polymorphism. Early identification of individuals presenting this genotype could be important to detect hypertension.