RAS Genetic Variants in Interaction with ACE Inhibitors Drugs Influences Essential Hypertension Control

Heidari, Farzad; Ramachandran, Vasudevan; Ali, Siti Zubaidah Mohd; Ismail, Patimah; Arkani, Mohammad

doi:10.1016/j.arcmed.2017.03.003

Cited by 18 publications

(17 citation statements)

References 36 publications

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“…However, conflicting results have been found regarding to the antihypertensive responses to ACE inhibitors or ARB. This is because the D allele was associated with better antihypertensive responses to these drugs in some studies,81,82 while the I allele was associated with those effects in others;83–85 in addition, several studies have shown no effects of this polymorphism on blood pressure responses to ACE inhibitors or ARB 86–89. Many factors, including study population, sample size, and possible interethnic differences in the distribution of I/D ACE polymorphism could explain these discrepancies.…”

Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin II mentioning

confidence: 99%

“…The AGT gene encodes angiotensinogen, and the most studied polymorphism of this gene is the SNP Met235Thr (rs699), which results in a threonine instead of a methionine in codon 235 of the protein 90. However, similar to the I/D polymorphism in ACE gene, there is no consensus regarding the effects of this polymorphism on the antihypertensive responses to ACE inhibitors or ARB 85,87–89,91,92. The CYP11b2 gene encodes aldosterone synthase, the enzyme that catalyzes the final step of aldosterone synthesis in juxtaglomerular cells 93.…”

Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin II mentioning

confidence: 99%

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<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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Hypertension is a multifactorial disease that affects approximately one billion subjects worldwide and is a major risk factor associated with cardiovascular events, including coronary heart disease and cerebrovascular accidents. Therefore, adequate blood pressure control is important to prevent these events, reducing premature mortality and disability. However, only one third of patients have the effective control of blood pressure, despite several classes of antihypertensive drugs available. These disappointing outcomes may be at least in part explained by interpatient variability in drug response due to genetic polymorphisms. To address the effects of genetic polymorphisms on blood pressure responses to the antihypertensive drug classes, studies have applied candidate genes and genome wide approaches. More recently, a third approach that considers gene-gene interactions has also been applied in hypertension pharmacogenomics. In this article, we carried out a comprehensive review of recent findings on the pharmacogenomics of antihypertensive drugs, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and calcium channel blockers. We also discuss the limitations and inconsistences that have been found in hypertension pharmacogenomics and the challenges to implement this valuable approach in clinical practice.

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Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin II mentioning

confidence: 99%

Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin II mentioning

confidence: 99%

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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“…Angiotensin-I converting enzyme (dipeptidyl carboxypeptidase, EC 3.4.15.1) belongs to the zinc-binding protease family [ 4 ]. This enzyme increases the production of angiotensin II by the renin-angiotensin system (RAS) [ 5 ], decreases the level of bradykinin produced by the kallikrein-kinin system (KKS) [ 6 ], and plays a critical physiological role in the regulation of peripheral blood pressure and electrolyte homeostasis. Therefore, a key to the treatment and prevention of hypertension is the effective inhibition of ACE activity [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Identification and Molecular Docking Study of a Novel Angiotensin-I Converting Enzyme Inhibitory Peptide Derived from Enzymatic Hydrolysates of Cyclina sinensis

Zhang

Luo

et al. 2018

Marine Drugs

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Marine-derived angiotensin-I converting enzyme (ACE) inhibitory peptides have shown potent ACE inhibitory activity with no side effects. In this study, we reported the discovery of a novel ACE-inhibitory peptide derived from trypsin hydrolysates of Cyclina sinensis (CSH). CSH was separated into four different molecular weight (MW) fractions by ultrafiltration. Fraction CSH-I showed the strongest ACE inhibitory activity. A peptide was purified by fast protein liquid chromatography (FPLC) and reversed-phase high-performance liquid chromatography (RP-HPLC) and its sequence was determined to be Trp-Pro-Met-Gly-Phe (WPMGF, 636.75 Da). The Lineweaver-Burk plot showed that WPMGF was a competitive inhibitor of ACE. WPMGF showed a significant degree of stability at varying temperatures, pH, and simulated gastrointestinal environment conditions. We investigated the interaction between this pentapeptide and ACE by means of a flexible molecular docking tool. The results revealed that effective interaction between WPMGF and ACE occurred mainly through hydrogen bonding, hydrophobic interactions, and coordination bonds between WPMGF and Zn(II). In conclusion, our study indicates that a purified extract derived from Cyclina sinensis or the WPMGF peptide could potentially be incorporated in antihypertensive functional foods or dietary supplements.

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“…EH is closely related to multiple factors, and statistics from studies at home and abroad shows that the influence of genetic factors on blood pressure accounts for 30%-50% of all their effects on the pathogenesis of EH. [1][2][3] The renin-angiotensin system (RAS) has significant functions in blood pressure regulation, electrolyte balance, vascular tension, and cardiovascular remodeling. As a membrane binding enzyme, ACE is located in vascular endothelial cells and widely distributed in the body.…”

Section: Discussionmentioning

confidence: 99%

“…The incidence rate of hypertension in children whose parents both suffer from the health problem can be as high as 46%, and about 60% of hypertensive patients can be asked about family history. 1–3…”

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Yi²,

Tang³

2021

J Renin Angiotensin Aldosterone Syst

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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.

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RAS Genetic Variants in Interaction with ACE Inhibitors Drugs Influences Essential Hypertension Control

Cited by 18 publications

References 36 publications

<p>Pharmacogenomics And Hypertension: Current Insights</p>

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Identification and Molecular Docking Study of a Novel Angiotensin-I Converting Enzyme Inhibitory Peptide Derived from Enzymatic Hydrolysates of Cyclina sinensis

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

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