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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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          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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            • Abstract: not found
            • Article: not found

            Point mutations of the human parathyroid calcium receptor gene are not responsible for non-suppressible renal hyperparathyroidism


              Author and article information

              S. Karger AG
              August 2000
              28 July 2000
              : 85
              : 4
              : 317-323
              aThird Division, Department of Medicine, Kobe University School of Medicine, Kobe, and bHattori Hospital, Miki, Japan
              45681 Nephron 2000;85:317–323
              © 2000 S. Karger AG, Basel

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              Figures: 3, Tables: 1, References: 27, Pages: 7
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