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      ACE I/D Gene Polymorphism Can't Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis

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          Abstract

          Background

          The results from the published studies on the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the treatment response to steroid in Asian children with idiopathic nephrotic syndrome (INS) is still conflicting. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and treatment response to steroid in Asian children and to explore whether ACE D allele or DD genotype could become a predictive marker for steroid responsiveness.

          Methodology/Principal Findings

          Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2010, and eligible investigations were synthesized using meta-analysis method. Five investigations were identified for the analysis of association between ACE I/D gene polymorphism and steroid-resistant nephrotic syndrome (SRNS) risk in Asian children and seven studies were included to explore the relationship between ACE I/D gene polymorphism and steroid-sensitive nephrotic syndrome (SSNS) susceptibility. Five investigations were recruited to explore the difference of ACE I/D gene distribution between SRNS and SSNS. There was no a markedly association between D allele or DD genotype and SRNS susceptibility or SSNS risk, and the gene distribution differences of ACE between SRNS and SSNS were not statistically significant. II genotype might play a positive role against SRNS onset but not for SSNS (OR = 0.51, P = 0.02; OR = 0.95, P = 0.85; respectively), however, the result for the association of II genotype with SRNS risk was not stable.

          Conclusions/Significance

          Our results indicate that D allele or DD homozygous can't become a significant genetic molecular marker to predict the treatment response to steroid in Asian children with INS.

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          Most cited references43

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          The renin–angiotensin system and diabetes: An update

          In the past few years the classical concept of the renin–angiotensin system (RAS) has experienced substantial conceptual changes. The identification of the renin/prorenin receptor, the angiotensin converting enzyme homologue ACE2 as an angiotensin peptide processing enzyme, Mas as a receptor for Ang-(1–7) and the possibility of signaling through ACE, have contributed to switch our understanding of the RAS from the classical limited proteolysis linear cascade to a cascade with multiple mediators, multiple receptors, and multi functional enzymes. In this review we will focus on the recent findings related to RAS and, in particular, on its role in diabetes by discussing possible interactions between RAS mediators, endothelium function, and insulin signaling transduction pathways as well as the putative role of ACE2-Ang-(1–7)-Mas axis in disease pathogenesis.
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            Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease.

            Angiotensin-converting enzyme 2 (ACE2) has recently emerged as a key regulator of the renin-angiotensin system in both health and disease. ACE2 deficiency is associated with elevated tissue and circulating levels of angiotensin II and reduced levels of angiotensin 1-7. Phenotypically, this results in a modest elevation in systolic blood pressure and left ventricular hypertrophy. In atherosclerosis-prone apolipoprotein E knockout mice, ACE2 deficiency results in augmented vascular inflammation and an inflammatory response that contributes to increased atherosclerotic plaque formation. In the kidney, ACE2 deficiency is associated with progressive glomerulosclerosis. Interventions such as ACE2 replenishment or augmentation of its actions have proven successful in reducing hypertension, plaque accumulation, and renal and cardiac damage in a range of different models. Although promising, the balance of the renin-angiotensin system remains complicated, with some evidence that overexpression of ACE2 may have adverse cardiac effects, and ACE2 and its metabolic products may promote epithelial-to-mesenchymal transition. Repletion of ACE2's activities offers a new strategy to complement current clinical interventions in treating hypertension, renal and cardiovascular disease. In particular conditions where ACE inhibition and angiotensin receptor blockade are partially effective, the adjunctive actions of ACE2 may not only reduce clinical escape but also augment the efficacy of interventions.
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              Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications

              Abstract The renin–angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type‐1 receptor (AT1) and, together with ACE, these components represent the ‘classical’ axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. In 2000, two groups using different methodologies identified a homolog of ACE, called ACE2, which cleaves Ang II to form the biologically active heptapeptide, Ang‐(1–7). Conceptually, ACE2, Ang‐(1–7), and its putative receptor, the mas receptor represent an ‘alternative’ axis of the RAS capable of opposing the often deleterious actions of Ang II. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. The present review focuses on the novel components and pathways of the RAS with particular reference to their potential contribution towards the pathophysiology of liver disease.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                18 May 2011
                : 6
                : 5
                : e19599
                Affiliations
                [1]Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, NanNing, China
                L' Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Italy
                Author notes

                Conceived and designed the experiments: T-BZ Y-HQ. Analyzed the data: T-BZ L-NS F-YL W-FH Y-JZ. Wrote the paper: T-BZ. Checked the data in the paper: Y-HQ L-NS F-YL W-FH.

                Article
                PONE-D-11-00591
                10.1371/journal.pone.0019599
                3097181
                21611163
                76aec9ec-9cae-44f7-a60d-aa9cdbca59a8
                Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 29 December 2010
                : 1 April 2011
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Genetics
                Population Genetics
                Genetic Polymorphism
                Population Biology
                Epidemiology
                Genetic Epidemiology
                Medicine
                Clinical Research Design
                Epidemiology
                Epidemiology
                Biomarker Epidemiology
                Genetic Epidemiology
                Nephrology
                Acute Renal Failure
                Chronic Kidney Disease
                Developmental Nephrology
                Geriatric Nephrology
                Hypertension
                Pediatric Nephrology
                Renal Transplantation
                Tubulointerstitial Disease

                Uncategorized
                Uncategorized

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