scholarly journals Genetic polymorphisms in the renin-angiotensin system and cognitive decline in Parkinson’s disease

2021 ◽  
Author(s):  
Anna Pierzchlińska ◽  
Jarosław Sławek ◽  
Monika Mak ◽  
Barbara Gawrońska-Szklarz ◽  
Monika Białecka
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Renin Angiotensin System ◽  
Nucleotide Polymorphisms ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
The Central Nervous System ◽  
The Impact

Abstract Background Renin-angiotensin system (RAS) influences the central nervous system not only through its peripheral impact—the brain possesses its own local RAS. Studies showed altered RAS components in Parkinson’s disease (PD) and their association with oxidative stress which may be linked to neurodegeneration and dementia. Moreover, the protective functions of RAS blockade antagonists against cognitive decline and dementia have been suggested. This study aimed to examine whether genetic variability in RAS genes correlates with cognitive decline in PD. Methods and results We genotyped single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT: rs699, rs4762), angiotensin II receptors (AGTR1: rs5186 and AGTR2: rs5194, rs1403543) genes, as well as insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE I/D) gene in 256 PD patients, divided into three groups: without cognitive decline, with mild cognitive impairment and with PD dementia. We did not find any significant differences in the frequencies of the analysed polymorphisms in any of the groups. Conclusions Despite no direct correlation between the investigated polymorphisms in RAS genes and cognitive decline in PD, we believe the impact of those genotypes may be indirect, affecting RAS blockade treatment.

Gene variants of the renin–angiotensin system and hypertension: from a trough of disillusionment to a welcome phase of enlightenment?

2010 ◽  
Vol 118 (8) ◽  
pp. 487-506 ◽  
Author(s):  
Gavin R. Norton ◽  
Richard Brooksbank ◽  
Angela J. Woodiwiss
Keyword(s):  
Association Studies ◽  
Large Population ◽  
Renin Angiotensin System ◽  
Human Populations ◽  
Incomplete Penetrance ◽  
Gene Variants ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
The Impact

There is substantial evidence to suggest that BP (blood pressure) is an inherited trait. The introduction of gene technologies in the late 1980s generated a sharp phase of over-inflated prospects for polygenic traits such as hypertension. Not unexpectedly, the identification of the responsible loci in human populations has nevertheless proved to be a considerable challenge. Common variants of the RAS (renin–angiotensin system) genes, including of ACE (angiotensin-converting enzyme) and AGT (angiotensinogen) were some of the first shown to be associated with BP. Presently, ACE and AGT are the only gene variants with functional relevance, where linkage studies showing relationships with hypertension have been reproduced in some studies and where large population-based and prospective studies have demonstrated these genes to be predictors of hypertension or BP. Nevertheless, a lack of reproducibility in other linkage and association studies has generated scepticism that only a concerted effort to attempt to explain will rectify. Without these explanations, it is unlikely that this knowledge will translate into the clinical arena. In the present review, we show that many of the previous concerns in the field have been addressed, but we also argue that a considerable amount of careful thought is still required to achieve enlightenment with respect to the role of RAS genes in hypertension. We discuss whether the previously identified problems of poor study design have been completely addressed with regards to the impact of ACE and AGT genes on BP. In the context of RAS genes, we also question whether the significance of ‘incomplete penetrance’ through associated environmental, phenotypic or physiological effects has been duly accounted for; whether appropriate consideration has been given to epistatic interactions between genes; and whether future RAS gene studies should consider variation across the gene by evaluating ‘haplotypes’.

scholarly journals High Order Gene-Gene Interactions in Eight Single Nucleotide Polymorphisms of Renin-Angiotensin System Genes for Hypertension Association Study

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Cheng-Hong Yang ◽  
Yu-Da Lin ◽  
Shyh-Jong Wu ◽  
Li-Yeh Chuang ◽  
Hsueh-Wei Chang
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Renin Angiotensin System ◽  
High Order ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
Snp Interaction

Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects. Here, we introduce an unbalanced function based on multifactor dimensionality reduction (MDR) for multiloci genotypes to detect high order gene-gene (SNP-SNP) interaction in unbalanced cases and controls of HT data. Eight SNPs of three RAS genes (angiotensinogen,AGT; angiotensin-converting enzyme,ACE; angiotensin II type 1 receptor,AT1R) in HT and non-HT subjects were included that showed no significant genotype differences. In 2- to 6-locus models of the SNP-SNP interaction, the SNPs ofAGTandACEgenes were associated with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%, confidence interval (CI) 1.26~6.21;P<0.005). In 7- and 8-locus model, SNP A1166C ofAT1Rgene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29;P<1.63E−08. In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models.AGT,ACE, andAT1Rgenes have overall effects with susceptibility to hypertension, where the SNPs ofACEhave a mainly hypertension-associated effect and show an interacting effect to SNPs ofAGTandAT1Rgenes.

scholarly journals The role of the central renin-angiotensin system in Parkinson’s disease

2009 ◽  
Vol 11 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Birgit Mertens ◽  
Patrick Vanderheyden ◽  
Yvette Michotte ◽  
Sophie Sarre
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Cardiovascular Disease, Single Nucleotide Polymorphisms; and the Renin Angiotensin System: Is There a MicroRNA Connection?

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Terry S. Elton ◽  
Sarah E. Sansom ◽  
Mickey M. Martin
Keyword(s):  
Cardiovascular Disease ◽  
Single Nucleotide Polymorphisms ◽  
Mirna Gene ◽  
Renin Angiotensin System ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
Inhibit Gene Expression

Essential hypertension is a complex disorder, caused by the interplay between many genetic variants, gene-gene interactions, and environmental factors. Given that the renin-angiotensin system (RAS) plays an important role in blood pressure (BP) control, cardiovascular regulation, and cardiovascular remodeling, special attention has been devoted to the investigation of single-nucleotide polymorphisms (SNP) harbored in RAS genes that may be associated with hypertension and cardiovascular disease. MicroRNAs (miRNAs) are a family of small,∼21-nucleotide long, and nonprotein-coding RNAs that recognize target mRNAs through partial complementary elements in the3′-untranslated region (3′-UTR) of mRNAs and inhibit gene expression by targeting mRNAs for translational repression or destabilization. Since miRNA SNPs (miRSNPs) can create, destroy, or modify miRNA binding sites, this review focuses on the hypothesis that transcribed target SNPs harbored in RAS mRNAs, that alter miRNA gene regulation and consequently protein expression, may contribute to cardiovascular disease susceptibility.

Menopause and Parkinson’s disease. Interaction between estrogens and brain renin-angiotensin system in dopaminergic degeneration

2016 ◽  
Vol 43 ◽  
pp. 44-59 ◽  
Author(s):  
Jose L. Labandeira-Garcia ◽  
Ana I. Rodriguez-Perez ◽  
Rita Valenzuela ◽  
Maria A. Costa-Besada ◽  
Maria J. Guerra
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Dopaminergic Degeneration

The role of the renin-angiotensin system in the pathogenesis of Parkinson’s disease

2021 ◽  
pp. 107-115
Author(s):  
Ю.Н. Быков ◽  
Н.А. Тетюшкин ◽  
В.А. Чипизубов ◽  
А.Н. Калягин ◽  
С.Ю. Лаврик
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Neurological Disorders ◽  
Renin Angiotensin System ◽  
Dopamine Level ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin

Введение. В настоящее время в научной литературе имеется большой объем данных, посвященных болезни Паркинсона. В то же время недостаточно освещена роль ренин-ангиотензиновой системы (РАС) в патогенезе заболевания. Цель - оценка современных патогенетически обоснованных подходов к терапии болезни Паркинсона. Методика. В базах данных Medline (PubMed) и eLibrary осуществлен подбор и анализ современных источников литературы, посвященных изучению роли ренин-ангиотензиновой системы в патогенезе болезни Паркинсона. Результаты. Болезнь Паркинсона является хроническим нейродегенеративным заболеванием, которое проявляется моторными и немоторными нарушениями. Анализ литературы показал, что помимо системной ренин-ангиотензиновой системы во многих тканях и органах имеется локальная РАС. Авторами было показано, что дофамин и ангиотензин II взаимодействуют в черной субстанции (SN) и стриатуме в реципрокном отношении. В модельных экспериментах на животных доказано, что снижение уровней дофамина сопровождается гиперактивацией ренин-ангиотензиновой системы. При этом так же отмечается выброс активных форм кислорода, индуцируемый микроглиальной тканью, и развитие нейровоспаления, что сопровождается нейродегенерацией. Применение блокаторов ангиотензиновых рецепторов в моделях на животных и в клинических испытаниях позволило значительно снизить прогрессирование нейродегенерации черной субстанции. Заключение. Авторами изложены результаты, свидетельствующие о том, что развитие болезни Паркинсона сопровождается гиперактивацией мозговой РАС. Подразумевается, что на новое звено патогенеза можно терапевтически воздействовать. Необходимы дополнительные исследования для понимания механизмов данных процессов. Background. A large amount of literature on Parkinson’s disease is currently available. However, the role of the renin-angiotensin system in the pathogenesis of this disease is not sufficiently covered. Aim. To highlight new therapeutic possibilities based on pathophysiological mechanisms of Parkinson’s disease. Methods. The literature retrieved from the PubMed, Medline, and eLibrary databases focusing on the role of the renin-angiotensin system in the pathogenesis of Parkinson’s disease was analyzed. Results. Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with persistent neurological disorders. Studies have demonstrated that a local renin-angiotensin system (RAS) exists in many tissues and organs along with the systemic RAS. The authors showed that dopamine and angiotensin II interact reciprocally in the substantia nigra (SN) and striatum. In animal models, a decrease in the dopamine level was accompanied by RAS overactivation. Furthermore, microglial tissue induced production of reactive oxygen species, which was associated with neuroinflammation. The angiotensin receptor blocker treatment used in animal models and clinical trials significantly reduced the progression of SN neurodegeneration. Conclusions. The authors reviewed the data of literature demonstrating that the progression of Parkinson’s disease is associated with overactivation of the cerebral RAS. Apparently, it is possible to influence therapeutically this new pathogenetic component of Parkinson’s disease. Further study is required for understanding the mechanisms of this process.

scholarly journals Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson’s Disease: The Role of Brain Renin Angiotensin System Components

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1669
Author(s):  
Tuladhar Sunanda ◽  
Bipul Ray ◽  
Arehally M. Mahalakshmi ◽  
Abid Bhat ◽  
Luay Rashan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Calcium Homeostasis ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

The past few decades have seen an increased emphasis on the involvement of the mitochondrial-associated membrane (MAM) in various neurodegenerative diseases, particularly in Parkinson’s disease (PD) and Alzheimer’s disease (AD). In PD, alterations in mitochondria, endoplasmic reticulum (ER), and MAM functions affect the secretion and metabolism of proteins, causing an imbalance in calcium homeostasis and oxidative stress. These changes lead to alterations in the translocation of the MAM components, such as IP3R, VDAC, and MFN1 and 2, and consequently disrupt calcium homeostasis and cause misfolded proteins with impaired autophagy, distorted mitochondrial dynamics, and cell death. Various reports indicate the detrimental involvement of the brain renin–angiotensin system (RAS) in oxidative stress, neuroinflammation, and apoptosis in various neurodegenerative diseases. In this review, we attempted to update the reports (using various search engines, such as PubMed, SCOPUS, Elsevier, and Springer Nature) demonstrating the pathogenic interactions between the various proteins present in mitochondria, ER, and MAM with respect to Parkinson’s disease. We also made an attempt to speculate the possible involvement of RAS and its components, i.e., AT1 and AT2 receptors, angiotensinogen, in this crosstalk and PD pathology. The review also collates and provides updated information on the role of MAM in calcium signaling, oxidative stress, neuroinflammation, and apoptosis in PD.

scholarly journals Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors

2020 ◽  
Vol 9 (11) ◽  
pp. 3472 ◽  
Author(s):  
Elena-Mihaela Cordeanu ◽  
Lucas Jambert ◽  
Francois Severac ◽  
Hélène Lambach ◽  
Jonathan Tousch ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Severe Pneumonia ◽  
University Hospital ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Previously Treated ◽  
The Impact ◽  
Harmful Effects ◽  
Observation Period

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

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