Association between angiotensin converting enzyme gene polymorphism and essential hypertension: A systematic review and meta-analysis.

BACKGROUND: The current meta-analytic study explored the relation between ACE gene insertion/deletion (I/D), and the risk of EH by reviewing relevant trials so as to determine the association between Angiotensin Converting Enzyme (ACE) gene polymorphism and essential hypertension (EH) susceptibility. METHODS: Relevant studies published before May 2019 were collected from the PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases. RESULTS: Fifty-seven studies involving a total of 32,862 patients were included. These studies found that ACE gene D allele was associated with higher EH susceptibility in allelic model, homozygote model, dominant model, and regressive model, and that Asian population with ACE gene D allele showed a higher EH susceptibility in all these models. Moreover, ACE gene D allele was found closely related to a higher EH susceptibility in the subgroups of HWE, NO HWE, Caucasian population, and Mixed population, with the majority being males in allelic model, homozygote model, and regressive model and the majority being females in allelic model. CONCLUSION: ACE gene D allele is associated with an overall higher EH susceptibility, which is confirmed in the subgroup analysis of Asian population, HWE, NO HWE, Caucasian population, and Mixed population.

Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China.

OBJECTIVE: Prolylcarboxypeptidase (PRCP) is both involved in the Kallikrein-Kinin system (KKS) and renin-angiotensin-aldosterone system (RAAS). This study aimed to determine the genetic impact of PRCP gene polymorphisms on essential hypertension (EH) in an isolated population from a remote region of China. METHODS: A haplotype-based study was investigated in 346 EH patients and 346 normal subjects and all samples were Hani minority residents in Southwest China. A total of 11 tag single nucleotide polymorphisms (SNPs) in PRCP gene were tested by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Single site analysis found that PRCP gene 3'UTR SNP rs3750931 was associated with EH. The minor allele G of rs3750931 was more prevalent in the EH patients compared to control subjects after Bonferroni correction (p < 0.05). Moreover, the rs3750931 G allele carriers showed higher average blood pressure (BP) level among the subjects. The H2 (GAGCACTAACA) haplotype without rs3750931 G allele showed the protective effect for EH (OR = 0.68, 95 CI 0.54-0.85, p = 0.001). CONCLUSION: The present study indicated PRCP gene rs3750931 was associated with the risk of EH. This SNP G allele could be considered as one of risk markers for EH in Hani population.

Endothelial Nitric Oxide Synthase Gene Polymorphisms (- 922A > G, - 786 T > C, Intron 4 b/a VNTR and 894 G > T) and Essential Hypertension: An Association Study with Haplotypes Analysis.

Endothelial Nitric Oxide Synthase (eNOS) is an indispensable regulator of blood pressure through producing Nitric Oxide (NO). There is some evidence to suggest that eNOS gene polymorphisms are associated with Essential Hypertension (EHT). In this study, the potential association between eNOS 4a/4b, A922G, G894T, T786C gene polymorphisms and EHT as individual risk factors and as haplotypes are examined in the southern population of Iran (Bandar-Abbas). In this study, 200 EHT patients and 200 normotensive subjects which were matched for age and sex were included. Genotyping was performed by either utilizing Polymerase Chain Reaction (PCR) or PCR followed by Restriction Fragment length Polymorphism (RFLP) method. Our results demonstrated statistically significant associations between T786C, G894T, and 4a/4a and EHT (p < 0.05); however, A922G had no significant association with EHT (p > 0.05). Haplotype analysis also suggested that - 786C/- 922A/4a, - 786C/- 922A/4b and - 786C/- 922G/4a haplotypes were more frequent in EHT group than control group, hypothesizing a positive association with EHT. The present study has identified that the eNOS genetic variations are associated with EHT in southern population of Iran (Bandar-Abbas). These findings also suggested that a number of haplotypes of eNOS gene may be a driving factor for EHT susceptibility in respected population.

Perinatal taurine exerts a hypotensive effect in male spontaneously hypertensive rats and down-regulates endothelial oxide nitric synthase in the aortic arch.

Essential hypertension is considered to be a result of the interaction between genetic and environmental factors, including perinatal factors. Different advantageous perinatal factors proved to have beneficial long-lasting effects against an abnormal genetic background. Taurine is a ubiquitous sulphur-containing amino acid present in foods such as seafood. The antihypertensive effects of taurine have been reported in experimental studies and in human hypertension. We aimed to investigate the effects of perinatal treatment with taurine in spontaneously hypertensive rats (SHR), a known model of genetic hypertension. Female SHR were administered with taurine (3 g/L) during gestation and lactation (SHR-TAU). Untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. Long-lasting effects in offspring were investigated. Addition of taurine to the mother's drinking water reduced blood pressure in adult offspring. No differences were observed in cardiac hypertrophy. Findings on morphometric evaluations suggest that perinatal treatment with taurine would be partially effective in improving structural alterations of the aorta. Modifications in gene expression of Bcl-2 family members and upregulation of endothelial nitric oxide synthase in the aorta of 22-week-old male offspring were found. No differences were observed on relative telomere length in different cardiovascular tissues between SHR and SHR-TAU. Altogether results suggest that taurine programming, albeit sex specific, is associated with gene expression changes which ultimately may lead to improvement of aortic remodelling and enhanced endothelial function because of augmented nitric oxide (NO) production.

Effect of Early Normotension with Olmesartan on Rho-kinase Activity in Hypertensive Patients.

BACKGROUND: Angiotensin II is a potent activator of the Rho-kinase (ROCK) pathway, through which it exerts some of its adverse vasoconstrictor effects. Clinical evidence on the effects of blocking the angiotensin II receptor 1 on ROCK activity in hypertensive patients is scarce. OBJECTIVE: To demonstrate that ROCK activity in peripheral blood mononuclear cells (PMBCs) in patients with essential hypertension is reduced earlier than previously observed, along with blood pressure (BP) lowering on treatment with olmesartan. METHODS: Prospective pilot open study; 17 hypertensive patients were treated with progressive olmesartan doses starting with 20 mg qd. BP was measured at 3, 6 and 9 weeks after treatment initiation. If treatment failed to normalize BP after 3 weeks, olmesartan dose was increased to 40 mg qd, and if still hypertensive after 6 weeks, 12.5 mg of hydrochlorothiazide qd was added. ROCK activity was measured at baseline and 9 weeks after treatment as myosin phosphatase target subunit 1 phosphorylation (MYPT1-p/T ratio) in PBMC. RESULTS: Mean baseline BP was 162 ± 4.9/101 ± 2.4 mmHg. After 9 weeks of treatment, both systolic and diastolic BP were reduced by 41 and 22 mmHg, respectively (p<0.05). Mean pretreatment MYPT1- p/T ratio in PMBCs was significantly reduced by 80% after 9 weeks with olmesartan (p<0.01). CONCLUSION: Normotension achieved after 9 weeks in 82% of the patients treated with olmesartan was associated with a significant reduction of ROCK activity in PBMC.

Human Erythrocyte Acetylcholinesterase in Health and Disease.

The biochemical properties of erythrocyte or human red blood cell (RBC) membrane acetylcholinesterase (AChE) and its applications on laboratory class and on research are reviewed. Evidence of the biochemical and the pathophysiological properties like the association between the RBC AChE enzyme activity and the clinical and biophysical parameters implicated in several diseases are overviewed, and the achievement of RBC AChE as a biomarker and as a prognostic factor are presented. Beyond its function as an enzyme, a special focus is highlighted in this review for a new function of the RBC AChE, namely a component of the signal transduction pathway of nitric oxide.

Association of CYP17A1 Genetic Polymorphisms and Susceptibility to Essential Hypertension in the Southwest Han Chinese Population.

BACKGROUND The CYP17A1 gene encodes for cytochrome P450 enzyme CYP17A1, which is involved with the steroidogenic pathway including mineralocorticoids. The CYP17A1 polymorphisms might affect enzyme activity, then leading to a state of mineralocorticoid 11-deoxycorticosterone excess characterized by hypertension, suppressed plasma renin activity, and low aldosterone concentrations. The aim of this study was to investigate the contribution of CYP17A1 polymorphisms in inducing the susceptibility to essential hypertension among the Southwest Han Chinese population. MATERIAL AND METHODS Eight single nucleotide polymorphisms of CYP17A1 were genotyped in a case-control study for samples by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS The polymorphisms rs11191548 and rs4919687 were significantly associated with hypertension risk, which was confirmed by systolic and diastolic blood pressure distribution analyses between different genotype groups, and these two polymorphisms were found in linkage disequilibrium. The rs4919687 polymorphism was estimated to cause the destruction of exonic splicing silencer (ESR and Motif 3) sites and to transform the transcription factor AREB6 binding site, respectively, in the bioinformatics analyses. The haplotypes rs4919686A-rs3740397G -rs4919687C-rs743572C-rs11191548C and rs4919686A-rs3740397G-rs4919687T-rs743572C- rs11191548T were found to be susceptible to essential hypertension. CONCLUSIONS Our findings suggest that the CYP17A1 polymorphisms could be a genetic risk factor for essential hypertension among the Yunnan Han Chinese population, which would have implications for the treatment of this complex disorder.

Association of the ace I/D gene polymorphism with DNA damage in hypertensive men.

The aim of the study was to evaluate the association between the angiotensin-converting enzyme ACE I/D (rs4340) polymorphism and DNA damage in pati-ents with essential hypertension (EH). The I/D polymorphism of ACE was determined by polymerase chain reaction in 170 male hypertensive patients and 64 normotensive blood donors. We used flow cytometry to determine the levels of cell death, micronuclei and accumulation of peripheral blood leukocytes in G1/G0, S, G2/M phases of the cell cycle. Additionally, the whole blood samples were incubated in vitro at 4 ºC for 24 h to investigate the genotype effects on the susceptibility of cells to DNA damage. We found lower frequency of cells in DNA synthesis S phase and higher levels of micronuclei in the hypertensive compared to normotensive group (p<0.05); increased formation of micronuclei was seen due to elevated micronuclei fre-quencies in patients with the ACE II genotype (p < 0.05), but not in ID or DD genotype carriers. Incubation of whole blood samples of normotensive individuals lead to the most active cell death (p < 0.05) and micronuclei formation (p > 0.05) in the II genotype carriers too. However, hypertensive patients displayed different cellular response to incubation-induced DNA damages in the ACE I/D genotype groups; after incubation, the frequencies of micronuclei were significantly higher in the DD genotype carriers (p < 0.05). To conclude, the study suggests that the ACE I/D polymorphism may contribute to mechanisms and intensity of DNA damages in hypertensive and normotensive individuals.