Alu insertion/deletion of ACE gene polymorphism might not affect significantly the serum bradykinin level in hypertensive patients taking ACE inhibitors

Widodo, Widodo; Wisnasari, Shila; Rohman, Mohammad Saifur; Yunita, Lowry; Lukitasari, Mifetika; Nuril, Maulidiyatun; Holil, Kholifah; Purwaningroom, Dian Laila

doi:10.1016/j.ejmhg.2016.08.001

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…A common insertion/deletion (I/D) of 287-bp in the Alu-sequence of intron 16, includes four individual SNPs (rs4646994, rs1799752, rs4340 and rs13447447) and modulates ACE1 expression ( Zhong et al, 2012 ). Alternative splicing caused by the presence of Alu-sequences, is responsible for the loss of one of the two active enzyme sites in the ACE1 I-allele, leaving the D-allele counterpart containing the two active sites favoring in turn the Ang-I to Ang-II conversion ( Purwaningroom et al, 2015 ; Widodo et al, 2017 ). Consequently, D/D genotype has the highest ACE1 activity, I/D genotype intermediate levels, and the I/I genotype the lowest ACE1 level ( Itoyama et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

et al. 2022

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SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication into the host cells. We also face the RAS-pathway unbalance triggered by virus-ACE2 interaction to discuss potential pharmacological and pharmacogenomics approaches aimed at restoring p53/NF-kB and ACE1/ACE2 balance to counteract the most severe forms of SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

et al. 2022

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“…In this study, the interactions between two ACE domains and four drugs that are registered in Poland as those that can be used in the treatment of diabetic nephropathy [46] were taken into account. It should be remembered here that the I allele of the rs4646994 polymorphism causes premature codon termination, resulting in the enzyme having only one active site in the N domain [12]. This means that potential drugs are able to attach to only one active site, which may affect their effectiveness.…”

Section: Discussionmentioning

confidence: 99%

“…However, the response to ACEi treatment varies among patients, often being unpredictable, partly due to genetic factors. The contribution of genetics to treatment response differences is primarily associated with the presence of polymorphisms, including single nucleotide polymorphisms (SNPs), insertions/deletions, and variable numbers of tandem repeats (VNTRs) [12,13]. Among the commonly used antihypertensive drugs for diabetic nephropathy treatment are ACEi, such as captopril, lisinopril, or ramipril [14].…”

Section: Introductionmentioning

confidence: 99%

“…The rs4646994 polymorphism in ACE causes premature codon termination, resulting in the enzyme having only one active site in the N domain, thereby limiting drug binding to a single site. In silico analysis is used to visualize and analyze the binding of individual ACEi drugs to these domains [12]. In patients with COVID-19, proteolytic enzymes may selectively affect ACE domains, leading to variable enzyme activity based on the rs4646994 genotype [13].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Angiotensin-Converting Enzyme (ACE) Polymorphisms in the Risk of Development and Treatment of Diabetic Nephropathy

Król-Kulikowska,

Abramenko,

Jakubek

et al. 2024

JCM

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Background: Angiotensin-converting enzyme (ACE) is responsible for the production of angiotensin II, and increased production of angiotensin II is observed in diabetes. What is more, ACE polymorphisms may play a role in the development of diabetic nephropathy. The aim of this study was to assess the role of selected ACE polymorphisms (rs4343 and rs4646994) in the risk of development of diabetic nephropathy and in the likelihood of renal replacement therapy. Methods: ACE polymorphisms were analyzed in a group of 225 patients who were divided into three subgroups. The rs4343 polymorphism was determined using the PCR-RFLP, and the rs4646994 polymorphism was determined using the PCR. Molecular docking between domains of ACE and its ligands was performed by using AutoDock Vina. Results: The G/G genotype of rs4343 polymorphism is associated with increased odds of developing diabetic nephropathy. The G allele is also associated with a higher risk of this disease. Similar results were obtained in patients who had already had a kidney transplant as a result of diabetic nephropathy. Conclusions: The presence of G/G and G/A genotypes, and the G allele increases the likelihood of developing diabetic nephropathy. This may also be a risk factor for renal replacement therapy.

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“…Interactions between receptors and ligand were analyzed by AutoDock Vina integrated in PyRx 0.8 ( ) ( 22 , 23 ). The docking method was used to evaluate binding affinities and to elucidate molecular mechanisms, and was performed according to previous literature ( 24 ). Docking was performed by setting receptors as rigid molecules and ligands as flexible molecules within the active site.…”

Section: Methodsmentioning

confidence: 99%

Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth

2018

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Ineffectiveness of cancer therapy may originate in the incompatibility of the treatment with various mutations in the cancer cells. Finding novel anticancer treatments that work efficiently for varying types of cancer cells remains challenging. Previous studies have identified that compounds in sea cucumbers are capable of inhibiting the growth of cancer cells and inducing apoptosis. However, information on the underlying mechanisms controlling cancer cell growth at a molecular level remains limited. The current study analyzed the potential of colochiroside A, ds-echinoside A, philinopside E, sphingosine and stichoposide C as inhibitors for anticancer target proteins, including mouse double minute 2 homolog (MDM2) and C-X-C chemokine receptor type 4 (CXCR4). Inhibition of MDM2 triggers apoptosis through regulation of tumor protein 53 and CXCR4 inhibition may prevent cancer cell proliferation and growth by affecting the Janus kinase 2/3 signal transducer and activator of transcription signaling pathway and protein tyrosine kinase 2. The results of a binding affinity analysis using molecular docking revealed that philinopside E and ds-echinoside A may inhibit MDM2 and CXCR4. The data suggested that these active compounds may be promising inhibitors of cell growth by binding to two targets simultaneously. Furthermore, stichoposide C and colochiroside A were predicted to inhibit CXCR4. Additional research is needed to validate the in vitro activity of the aforementioned compounds.

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Alu insertion/deletion of ACE gene polymorphism might not affect significantly the serum bradykinin level in hypertensive patients taking ACE inhibitors

Cited by 7 publications

References 20 publications

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

The Role of Angiotensin-Converting Enzyme (ACE) Polymorphisms in the Risk of Development and Treatment of Diabetic Nephropathy

Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth

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