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.

Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC: Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 1993;366:575–580.
Pollak MR, Brown EM, Chou YH, Hebert SC, Marx SJ, Steinmann B, Levi T, Seidman CE, Seidman JG: Mutations in the human Ca2+-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell 1993;75:1297–1303.
Pearce SH, Trump D, Wooding C, Besser GM, Chew SL, Grant DB, Heath DA, Hughes IA, Paterson CR, Whyte MP: Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells. J Clin Invest 1995;96:2683–2692.
Lovlie R, Eiken HG, Sorheim JI, Boman H: The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism. Hum Genet 1996;98:129–133.
Chattopadhyay N, Mithal A, Brown EM: The calcium-sensing receptor: A window into the physiology and pathophysiology of mineral ion metabolism. Endocr Rev 1996;17:289–307.
Ho C, Conner DA, Pollak MR, Ladd DJ, Kifor O, Warren HB, Brown EM, Seidman JG, Seidman CE: A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat Genet 1995;11:389–394.
Heath H, Odelberg S, Jackson CE; Teh BT, Hayward N, Larsson C, Buist NRM, Krapcho KJ, Hung BC, Capuano IV, Garrett JE, Leppert MF: Clustered inactivating mutations and benign polymorphisms of the calcium receptor gene in familial benign hypocalciuric hypercalcemia suggest receptor functional domains. J Clin Endocrinol Metab 1996;81:1312–1317.
Tsukamoto Y, Heishi M, Nagaba Y, Kobayashi N, Nomura Y, Takahashi K, Tazawa H: More on hyperparathyroidism and the vitamin D receptor. Nat Med 1996;2:1162.
Yokoyama K, Shigematsu T, Tsukada T, Ogura Y, Takemoto F, Hara S, Yamada A, Kawaguchi Y, Hosoya T: Apa I polymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease. Kidney Int 1998;53:454–458.
Nagaba Y, Heishi M, Tazawa H, Tsukamoto Y, Kobayashi Y: Vitamin D receptor gene polymorphisms affect secondary hyperparathyroidism in hemodialyzed patients. Am J Kidney Dis 1998;32:464–469.
Payne RB, Little AJ, Williams RB, Milner JR: Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J 1973;iv:643–646.
Frolich M, Walma ST, Paulson C, Papapoulos SE: Immunoradiometric assay for intact human parathyroid hormone: Characteristics, clinical application and comparison with a radio-immunoassay. Ann Clin Biochem 1990;27:69–72.
Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning: A Laboratory Manual, ed 2. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, 1989.
Tokita A, Matsumoto H, Morrison NA, Tawa T, Miura Y, Fukamauchi K, Mitsuhashi N, Irimoto M, Yamamori S, Miura M, Watanabe T, Kuwabara Y, Yabuta K, Eisman JA: Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women. J Bone Miner Res 1996;11:1003–1009.
McNair P, Christensen MS, Madsbad S, Christiansen C, Transbol I: Hypoparathyroidism in diabetes mellitus. Acta Endocrinol (Copenh) 1981;96:81–86.
Cruikshank DP, Pitkin RM, Reynolds WA, Williams GA, Hargis GK: Altered maternal calcium homeostasis in diabetic pregnancy. J Clin Endocrinol Metab 1980;50:264–267.
Vincenti F, Arnaud SB, Recker R, Genant H, Amend W Jr, Feduska NJ, Salvatierra O Jr: Parathyroid and bone response of the diabetic patient to uremia. Kidney Int 1984;25:677–682.
Sugimoto T, Ritter C, Morrissey J, Hayes C, Slatopolsky E: Effects of high concentrations of glucose on PTH secretion in parathyroid cells. Kidney Int 1990;37:1522–1527.
Piraino BM, Rault R, Dominguez JH, Puschett JB: Renal osteodystrophy in patients on hemodialysis for more than 10 years. Miner Electrolyte Metab 1986;12:390–396.
Eisenberg B, Tzamaloukas AH, Murata GH, Elliott TM, Jackson JE: Factors affecting bone mineral density in elderly men receiving chronic in-center hemodialysis. Clin Nucl Med 1991;16:30–36.
Pei Y, Hercz G, Greenwood C, Segre G, Manuel A, Saiphoo C, Fenton S, Sherrard D: Renal osteodystrophy in diabetic patients. Kidney Int 1993;44:159–164.
Brown EM: Extracellular sensing, regulation of parathyroid cell function and role of calcium and other ions as extracellular (first) messengers. Physiol Rev 1991;71:371–411.
Slatopolsky E, Finch J, Denda M, Ritter C, Zhong M, Dusso A, MacDonald PN, Brown AJ: Phosphorus restriction prevents parathyroid gland growth: High phosphorus directly stimulates PTH secretion in vitro. J Clin Invest 1996;97:2534–2540.
Almaden Y, Canalejo A, Hernandez A, Ballesteros E, Garcia-Navarro S, Torres A, Rodriguez M: Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro. J Bone Miner Res 1996;11:970–976.
Degenhardt S, Toell A, Weidemann W, Dotzenrath C, Spindler KD, Grabensee B: Point mutations of the human parathyroid calcium receptor gene are not responsible for non-suppressible renal hyperparathyroidism. Kidney Int 1998;53:556–561.
Janicic N, Pausova Z, Cole DE, Hendy GN: Insertion of an Alu sequence in the Ca(2+)-sensing receptor gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Am J Hum Genet 1995;56:880–886.
Bai M, Janicic N, Trivedi S, Quinn SJ, Cole DE, Brown EM, Hendy GN: In vivo and in vitro characterization of neonatal hyperparathyroidism resulting from a de novo, heterozygous mutation in the Ca2+-sensing receptor gene: Normal maternal calcium homeostasis as a cause of secondary hyperparathyroidism in familial benign hypocalciuric hypercalcemia. J Clin Invest 1997;99:1917–1925.
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.