Dataset Information

Association of -344C/T polymorphism in the aldosterone synthase (CYP11B2) gene with cardiac and cerebrovascular events in Chinese patients with hypertension.

ABSTRACT: OBJECTIVE:Several recent studies have shown that the aldosterone synthase gene (CYP11B2) -344C/T polymorphism is related to cardiovascular diseases. However, whether the -344C allele influences the incidence of cardiovascular diseases in Chinese patients with hypertension is unclear. METHODS:Chinese patients with essential hypertension were genotyped for the -344C/T polymorphism in CYP11B2 (n?=?755; CC, n?=?112; CT, n?=?361; TT, n?=?282) and followed for 11 years for major adverse cardiovascular events (MACEs), including stroke, onset of coronary artery disease (CAD), and CAD-related death. Established cardiovascular risk factors were used to adjust the multivariate Cox analysis. RESULTS:After a mean follow-up period of 7.60?±?1.12 years, a significantly higher incidence of MACEs was seen in patients with the CC genotype than in those with the CT and TT genotypes. The CC variant was significantly and independently predictive of MACEs (hazard ratio?=?2.049), CAD (hazard ratio?=?1.754), and stroke (hazard ratio?=?2.588), but not CAD-related stroke or death. CONCLUSION:The CYP11B2 -344 CC genotype is a risk factor for CAD and stroke, independent of other established cardiovascular risk factors in Chinese patients with hypertension.

SUBMITTER: Wang L

PROVIDER: S-EPMC7503017 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of -344C/T polymorphism in the aldosterone synthase (CYP11B2) gene with cardiac and cerebrovascular events in Chinese patients with hypertension.

Wang Lili L Zhang Zhi Z Liu Dongxia D Yuan Kexin K Zhu Guohua G Qi Xiaoyong X

The Journal of international medical research 20200901 9

<h4>Objective</h4>Several recent studies have shown that the aldosterone synthase gene (<i>CYP11B2</i>) -344C/T polymorphism is related to cardiovascular diseases. However, whether the -344C allele influences the incidence of cardiovascular diseases in Chinese patients with hypertension is unclear.<h4>Methods</h4>Chinese patients with essential hypertension were genotyped for the -344C/T polymorphism in <i>CYP11B2</i> (n = 755; CC, n = 112; CT, n = 361; TT, n = 282) and followed for 11 years for ...[more]

PMID: 32938270

Similar Datasets

Project description: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.

Project description:BackgroundAldosterone synthase (CYP11B2) deficiency is a rare autosomal recessive disorder, usually presenting with severe salt-wasting in infancy or stress-induced hyperkalaemia and postural hypotension in adulthood. Neonatal screening for congenital adrenal hyperplasia, another cause of salt wasting, using 17-hydroxyprogesterone measurement would fail to detect aldosterone synthase deficiency, a diagnosis which may be missed until the patient presents with salt-wasting crisis. Due to this potential life-threatening risk, comprehensive hormonal investigation followed by genetic confirmation for suspected patients would facilitate clinical management of the patient and assessment of the genetic implication in their offspring.Case presentationWe describe a 33-year old Chinese man who presented in infancy with life-threatening hyponatraemia and failure to thrive, but remained asymptomatic on fludrocortisone since. Chromosomal analysis confirmed a normal male karyotype of 46, XY. Plasma steroid profile showed high plasma renin activity, low aldosterone level, and elevated 18-hydroxycorticosterone, compatible with type 2 aldosterone synthase deficiency. The patient was heterozygous for a novel CYP11B2 mutation: c.977C > A (p.Thr326Lys) in exon 3. He also carried a heterozygous mutation c.523_525delAAG (p.Lys175del) in exon 6, a known pathogenic mutation causing aldosterone synthase deficiency. Sequencing of CYP11B2 in his parents demonstrated that the mother was heterozygous for c.977C > A, and the father was heterozygous for c.523_525delAAG.ConclusionAlthough a rare cause of hyperreninaemic hypoaldosteronism, aldosterone synthase deficiency should be suspected and the diagnosis sought in patients who present with life-threatening salt-wasting in infancy, as it has a good long-term prognosis when adequate fludrocortisone replacement is instituted. To our knowledge, this is the first Chinese patient in which the molecular basis of aldosterone synthase deficiency has been identified.

Project description:Psoriasis is a common autoimmune-mediated chronic, inflammatory skin disease. Although, the molecular mechanism is not completely understood, psoriasis is caused by genetic and non-genetic parameters. The current study aimed (1) to define genotype and allele frequency of endothelial nitric oxide synthase (eNOS Glu298Asp) gene polymorphism in hypertensive and/or non-hypertensive psoriatic patients (2) to investigate the possible relationship between the eNOS Glu298Asp polymorphism and the risk of hypertension among psoriatic patients in the Turkish population.This cross-sectional, case-control study was performed between March 2010 and November 2012 at the University hospital in Çanakkale, Turkey Patients and Methods: Gene profiles of 75 psoriatic patients (21 hypertensive and 54 normotensive pa.tients) and 55 healthy (normotensive and non-psoriatic) volunteers were compared. Peripheral blood-EDTA samples were used for total genomic DNA isolation and genotyping. Target eNOS gene was genotyped for patients and control groups by real-time PCR melting-curve analysis system (LightCycler 2.0,Roche, Germany, and results were compared statistically.An increased T allele frequency in eNOS Glu298Asp single-nucleotide polymorphism (SNP) was determined in psoriatic patients when compared with normotensive non-psoriatic healthy volunteers (OR 2.3, CI 1.14-3.99), (P=.017). The T allele frequency was also found to be increased in hypertensive psoriatic patients when compared with healthy volunteers (4.83-fold increased, 95% CI 1.62-14.43 ([P=.003]) and normotensive psoriatic patients (3.03-fold increased, 95% CI 1.03-8.94 [P=.041]), respectively.The current preliminary results suggested that there was a correlation between eNOS Glu298Asp polymorphism and hypertension among psoriatic patients in the Turkish population. The T allele frequency of eNOS Glu298Asp SNP was different in hypertensive psoriatic patients, and the difference was statistically significant when compared with the normotensive psoriatic patients and healthy controls. These results need to be confirmed by large-scale studies.

Dataset Information

Association of -344C/T polymorphism in the aldosterone synthase (CYP11B2) gene with cardiac and cerebrovascular events in Chinese patients with hypertension.

Publications

Association of -344C/T polymorphism in the aldosterone synthase (CYP11B2) gene with cardiac and cerebrovascular events in Chinese patients with hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets