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      Association of Polymorphic Alleles of the Calcium-Sensing Receptor Gene with Parathyroid Hormone Secretion in Hemodialysis Patients

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          Abstract

          The present study was performed to investigate the association of calcium-sensing receptor (CaSR) genotypes with parathyroid hormone (PTH) secretion in hemodialysis patients. Subjects were 122 Japanese hemodialysis patients, including 39 patients with diabetes mellitus (DM). The CaSR polymorphisms tested were codon 990 in intracellular domain (A/A, A/G, and G/G groups) as well as T to C base change of intron 4 (T/T, T/C, and C/C groups). Statistical analysis of these polymorphisms revealed that the serum PTH level was significantly higher in the A/A group than in the G/G group in the former. In addition, the serum PTH level was also significantly higher in patients displaying C allele, as compared with the T/T group in the latter. This association of two polymorphisms with the serum PTH level was observed only in non-DM patients. Although two polymorphisms affected the PTH level independently, patients who possessed both genotypes (AAC+) had a markedly high level of PTH not only in the non-DM group but also in the DM group. The present findings indicate the possibility of the prediction for the extensive progression of secondary hyperparathyroidism through analyzing the CaSR polymorphisms in chronic hemodialysis patients.

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          Most cited references 2

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          Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.

          Maintenance of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion. The latter restores normocalcaemia by acting on kidney and bone. We now report the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.
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            Point mutations of the human parathyroid calcium receptor gene are not responsible for non-suppressible renal hyperparathyroidism

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              Author and article information

              Journal
              NEF
              Nephron
              10.1159/issn.1660-8151
              Nephron
              S. Karger AG
              1660-8151
              2235-3186
              2000
              August 2000
              28 July 2000
              : 85
              : 4
              : 317-323
              Affiliations
              aThird Division, Department of Medicine, Kobe University School of Medicine, Kobe, and bHattori Hospital, Miki, Japan
              Article
              45681 Nephron 2000;85:317–323
              10.1159/000045681
              10940742
              © 2000 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: 3, Tables: 1, References: 27, Pages: 7
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/45681
              Categories
              Original Paper

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