Gene, Cell and Tissue

Published by: Kowsar

Gain-of-Function R990G Polymorphism of the Calcium-Sensing Receptor Gene: Gender-Related Effects in Patients with Coronary Heart Disease

Ezgi Irmak Aslan 1 , Ender Coskunpinar 2 , Ozlem Kurnaz Gomleksiz 3 , Ozan Tiryakioglu 4 , Zehra Bugra 5 , Oguz Ozturk 1 and Hulya Yılmaz Aydogan 1 , *
Authors Information
1 Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
2 Department of Medical Biology, Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
3 Department of Medical Biology, Faculty of Medicine, Altinbas University, Istanbul, Turkey
4 Department of Nutrition and Dietetics, School of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey
5 Department of Cardiology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
Article information
  • Gene, Cell and Tissue: April 2018, 5 (2); e79164
  • Published Online: July 18, 2018
  • Article Type: Research Article
  • Received: May 19, 2018
  • Revised: June 26, 2018
  • Accepted: July 11, 2018
  • DOI: 10.5812/gct.79164

To Cite: Aslan E I, Coskunpinar E, Kurnaz Gomleksiz O, Tiryakioglu O, Bugra Z, et al. Gain-of-Function R990G Polymorphism of the Calcium-Sensing Receptor Gene: Gender-Related Effects in Patients with Coronary Heart Disease, Gene Cell Tissue. 2018 ; 5(2):e79164. doi: 10.5812/gct.79164.

Copyright © 2018, Gene, Cell and Tissue. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Hauache OM. Extracellular calcium-sensing receptor: structural and functional features and association with diseases. Braz J Med Biol Res. 2001;34(5):577-84. [PubMed: 11323743].
  • 2. Ziegelstein RC, Xiong Y, He C, Hu Q. Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells. Biochem Biophys Res Commun. 2006;342(1):153-63. doi: 10.1016/j.bbrc.2006.01.135. [PubMed: 16472767].
  • 3. Molostvov G, James S, Fletcher S, Bennett J, Lehnert H, Bland R, et al. Extracellular calcium-sensing receptor is functionally expressed in human artery. Am J Physiol Renal Physiol. 2007;293(3):F946-55. doi: 10.1152/ajprenal.00474.2006. [PubMed: 17537980].
  • 4. Ward BK, Magno AL, Walsh JP, Ratajczak T. The role of the calcium-sensing receptor in human disease. Clin Biochem. 2012;45(12):943-53. doi: 10.1016/j.clinbiochem.2012.03.034. [PubMed: 22503956].
  • 5. Ortiz-Capisano MC, Ortiz PA, Garvin JL, Harding P, Beierwaltes WH. Expression and function of the calcium-sensing receptor in juxtaglomerular cells. Hypertension. 2007;50(4):737-43. doi: 10.1161/HYPERTENSIONAHA.107.095158. [PubMed: 17785631].
  • 6. Smajilovic S, Tfelt-Hansen J. Novel role of the calcium-sensing receptor in blood pressure modulation. Hypertension. 2008;52(6):994-1000. doi: 10.1161/HYPERTENSIONAHA.108.117689. [PubMed: 18955662].
  • 7. Maillard MP, Tedjani A, Perregaux C, Burnier M. Calcium-sensing receptors modulate renin release in vivo and in vitro in the rat. J Hypertens. 2009;27(10):1980-7. doi: 10.1097/HJH.0b013e32832f0d22. [PubMed: 19593209].
  • 8. Atchison DK, Ortiz-Capisano MC, Beierwaltes WH. Acute activation of the calcium-sensing receptor inhibits plasma renin activity in vivo. Am J Physiol Regul Integr Comp Physiol. 2010;299(4):R1020-6. doi: 10.1152/ajpregu.00238.2010. [PubMed: 20660105]. [PubMed Central: PMC2957381].
  • 9. Molostvov G, Fletcher S, Bland R, Zehnder D. Extracellular calcium-sensing receptor mediated signalling is involved in human vascular smooth muscle cell proliferation and apoptosis. Cell Physiol Biochem. 2008;22(5-6):413-22. doi: 10.1159/000185484. [PubMed: 19088423].
  • 10. Alam MU, Kirton JP, Wilkinson FL, Towers E, Sinha S, Rouhi M, et al. Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells. Cardiovasc Res. 2009;81(2):260-8. doi: 10.1093/cvr/cvn279. [PubMed: 18852253].
  • 11. Molostvov G, Hiemstra TF, Fletcher S, Bland R, Zehnder D. Arterial Expression of the Calcium-Sensing Receptor Is Maintained by Physiological Pulsation and Protects against Calcification. PLoS One. 2015;10(10). e0138833. doi: 10.1371/journal.pone.0138833. [PubMed: 26436544]. [PubMed Central: PMC4593585].
  • 12. Marz W, Seelhorst U, Wellnitz B, Tiran B, Obermayer-Pietsch B, Renner W, et al. Alanine to serine polymorphism at position 986 of the calcium-sensing receptor associated with coronary heart disease, myocardial infarction, all-cause, and cardiovascular mortality. J Clin Endocrinol Metab. 2007;92(6):2363-9. doi: 10.1210/jc.2006-0071. [PubMed: 17374704].
  • 13. Jung J, Foroud TM, Eckert GJ, Flury-Wetherill L, Edenberg HJ, Xuei X, et al. Association of the calcium-sensing receptor gene with blood pressure and urinary calcium in African-Americans. J Clin Endocrinol Metab. 2009;94(3):1042-8. doi: 10.1210/jc.2008-1861. [PubMed: 19066294]. [PubMed Central: PMC2681276].
  • 14. Schepelmann M, Yarova PL, Lopez-Fernandez I, Davies TS, Brennan SC, Edwards PJ, et al. The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. Am J Physiol Cell Physiol. 2016;310(3):C193-204. doi: 10.1152/ajpcell.00248.2015. [PubMed: 26538090]. [PubMed Central: PMC5243220].
  • 15. Han G, Wang O, Nie M, Zhu Y, Meng X, Hu Y, et al. Clinical phenotypes of Chinese primary hyperparathyroidism patients are associated with the calcium-sensing receptor gene R990G polymorphism. Eur J Endocrinol. 2013;169(5):629-38. doi: 10.1530/EJE-13-0441. [PubMed: 23946278].
  • 16. Vezzoli G, Terranegra A, Arcidiacono T, Biasion R, Coviello D, Syren ML, et al. R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria. Kidney Int. 2007;71(11):1155-62. doi: 10.1038/ [PubMed: 17332735].
  • 17. Turkmen F, Ozdemir A, Sevinc C, Eren PA, Demiral S. Calcium-sensing receptor gene polymorphisms and cardiac valvular calcification in patients with chronic renal failure: a pilot study. Hemodial Int. 2009;13(2):176-80. doi: 10.1111/j.1542-4758.2009.00333.x. [PubMed: 19432691].
  • 18. Shakhssalim N, Kazemi B, Basiri A, Houshmand M, Pakmanesh H, Golestan B, et al. Association between calcium-sensing receptor gene polymorphisms and recurrent calcium kidney stone disease: a comprehensive gene analysis. Scand J Urol Nephrol. 2010;44(6):406-12. doi: 10.3109/00365599.2010.497770. [PubMed: 20602573].
  • 19. Hibler EA, Hu C, Jurutka PW, Martinez ME, Jacobs ET. Polymorphic variation in the GC and CASR genes and associations with vitamin D metabolite concentration and metachronous colorectal neoplasia. Cancer Epidemiol Biomarkers Prev. 2012;21(2):368-75. doi: 10.1158/1055-9965.EPI-11-0916. [PubMed: 22144504]. [PubMed Central: PMC3275650].
  • 20. Shui IM, Mucci LA, Wilson KM, Kraft P, Penney KL, Stampfer MJ, et al. Common genetic variation of the calcium-sensing receptor and lethal prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2013;22(1):118-26. doi: 10.1158/1055-9965.EPI-12-0670-T. [PubMed: 23125333]. [PubMed Central: PMC3538912].
  • 21. He YH, Kong WL, Wang G, Zhao Y, Bi MX, Na LX, et al. The calcium-sensing receptor R990G polymorphism is associated with increased risk of hypertriglyceridemia in obese Chinese. Gene. 2014;533(1):67-71. doi: 10.1016/j.gene.2013.09.122. [PubMed: 24120622].
  • 22. Breum Jakobsen NF, Laugesen E, Rolighed L, Nissen PH, Poulsen PL, Pedersen EB, et al. The cardiovascular system in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene. Eur J Endocrinol. 2016;175(4):299-309. doi: 10.1530/EJE-16-0369. [PubMed: 27418061].

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