Blog
About

0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      The Decorin Gene 179 Allelic Variant Is Associated with a Slower Progression of Renal Disease in Patients with Type 1 Diabetes

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background genetic factors may influence the variability in the rate of progression of kidney disease in type 1 diabetes. In diabetes, progressive mesangial matrix expansion and glomerular sclerosis are, to a large extent, mediated by TGF-β1. Decorin, a proteoglycan which is a component of the extracellular matrix, regulates TGF-β1 activity and expression. We have examined the relationship between the 179/183/185 polymorphism of the Decorin gene and the progression of diabetic nephropathy. Methods: From a cohort of 175 European patients with diabetic nephropathy, we studied 79 patients who were selected because they had a follow-up of at least 2 years (average 6.5 years; range: 2.5–15 years), and regular measurements of serum creatinine on 5 or more occasions. Creatinine clearance (CrCl) calculated from serum creatinine concentration was used as a measure of derived glomerular filtration rate (dGFR). All patients were on antihypertensive therapy. Results: The rate of dGFR decline in the whole cohort was [median (range)] 4.6 (–3.8 to 18) ml/min/year. No patient with 185 allele was found. Patients with 179/183 and 179/179 genotype (n = 14), who were considered together and named 179 carriers, had a slower rate of GFR decline [2.1 (0.06–11.7) ml/min/year] as compared to patients with Decorin 183/183 genotype (n = 65) [5.6 (–3.8 to 18) ml/min/year; p < 0.001]. In addition, when considering individual data, patients carrying the 179 allele had a 3.0 (95%CI: 1.8–4.2)-fold higher probability to be slow progressors (i.e. GFR decline below the median). This difference could not be accounted for by differences in duration of disease, type and duration of antihypertensive therapy, albumin excretion rate, blood glucose or blood pressure control. In a multivariate logistic analysis albumin excretion rate (p < 0.001), mean arterial pressure (p = 0.07) and Decorin gene polymorphism (p = 0.036), but not HbA1c, were independently correlated with the rate of dGFR fall. Conclusion: The 179 allele variant of the Decorin gene is related to a slower progression of DN in type 1 diabetic patients with albuminuria and receiving antihypertensive therapy.

          Related collections

          Most cited references 5

          • Record: found
          • Abstract: not found
          • Article: not found

          Pathophysiology of progressive nephropathies.

           T Bertani,  G. Remuzzi (1998)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Negative regulation of transforming growth factor-beta by the proteoglycan decorin.

            Decorin is a small chondroitin-dermatan sulphate proteoglycan consisting of a core protein and a single glycosaminoglycan chain. Eighty per cent of the core protein consists of 10 repeats of a leucin-rich sequence of 24 amino acids. Similar repeats have been found in two other proteoglycans, biglycan and fibromodulin, and in several other proteins including Drosophila morphogenetic proteins. Expression of high levels of decorin in Chinese hamster ovary cells has a dramatic effect on their morphology and growth properties. We now report that this effect is due at least in part to the ability of decorin to bind transforming growth factor-beta, an autocrine factor that stimulates the growth of Chinese hamster ovary cells. As transforming growth factor-beta induces synthesis of decorin in many cell types, our results suggest that decorin may be a component of a feedback system regulating cell growth.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Genetics of diabetic nephropathy: evidence for major and minor gene effects.

               A Krolewski (1999)
                Bookmark

                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2002
                September 2002
                14 August 2002
                : 92
                : 1
                : 72-76
                Affiliations
                aClinicaland Research Unit of Endocrinology, Scientific Institute ‘Casa Sollievo della Sofferenza’ San Giovanni Rotondo (FG); bDiabetes Unit, Hospital ‘Brotzu’, Cagliari; cChair of Metabolic Medicine, University of Padova, Padova; dInstitute of Internal Medicine, Turin, Italy; eUnit for Metabolic Medicine, Department of Endocrinology Diabetes and Internal Medicine, GKT School of Medicine, King’s College London, Guy’s Hospital, London, UK; fDepartment of Clinical Science, University ‘La Sapienza’, Rome, Italy
                Article
                64470 Nephron 2002;92:72–76
                10.1159/000064470
                12187087
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 1, References: 29, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/64470
                Categories
                Original Paper

                Comments

                Comment on this article