{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:38:58Z","timestamp":1786372738808,"version":"build-2736575974"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the calcium-sensing receptor (\n                      <jats:italic toggle=\"yes\">CASR<\/jats:italic>\n                      ) alter the response to the calcimimetic cinacalcet.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      We analyzed DNA samples in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, a randomized trial comparing cinacalcet to placebo on a background of usual care. Of the 3883 patients randomized, 1919 (49%) consented to DNA collection, and samples from 1852 participants were genotyped for 18\n                      <jats:italic toggle=\"yes\">CASR<\/jats:italic>\n                      polymorphisms. The European ancestry (EA;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =1067) and African ancestry (AfAn;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =405) groups were assessed separately. SNPs in\n                      <jats:italic toggle=\"yes\">CASR<\/jats:italic>\n                      were tested for their association with biochemical measures of mineral metabolism at baseline, percent change from baseline to 20 weeks, and risk of clinical fracture as dependent variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were modest associations of\n                      <jats:italic toggle=\"yes\">CASR<\/jats:italic>\n                      SNPs with increased baseline serum parathyroid hormone and bone alkaline phosphatase primarily with the minor allele in the EA group (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u22640.03), but not in the AfAn sample. In contrast, there was a modest association of decreased baseline serum calcium and FGF23 with\n                      <jats:italic toggle=\"yes\">CASR<\/jats:italic>\n                      SNPs (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04) primarily with the minor allele in the AfAn but not in the EA sample. The minor allele of two SNPs was associated with decreased percent reduction in parathyroid hormone from baseline to 20 weeks in the EA population (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.04) and this was not altered with cinacalcet. In both EA and AfAn, the same SNP (rs9740) was associated with decreased calcium with cinacalcet treatment (EA and AfAn\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u22640.03). Three SNPs in high linkage disequilibrium were associated with a higher risk of clinical fracture that was attenuated by cinacalcet treatment in the EA sample (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These modest associations, if validated, may provide explanations for differences in CKD\u2013mineral bone disorder observed in EA and AfAn populations, and for differential biochemical responses to calcimimetics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.11141016","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T20:20:17Z","timestamp":1497903617000},"page":"1128-1138","source":"Crossref","is-referenced-by-count":25,"title":["Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing Hemodialysis"],"prefix":"10.2215","volume":"12","author":[{"given":"Sharon M.","family":"Moe","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine and"},{"name":"Department of Medicine, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Wetherill","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian Scott","family":"Decker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongbing","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Long","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Vatta","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana M.","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn M.","family":"Chertow","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,6,19]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1053\/j.ackd.2006.10.005","article-title":"Chronic kidney disease-mineral-bone disorder: A new paradigm.","volume":"14","author":"Moe","year":"2007","journal-title":"Adv Chronic Kidney Dis"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1038\/sj.ki.5000414","article-title":"Definition, evaluation, and classification of renal osteodystrophy: A position statement from kidney disease: Improving Global Outcomes (KDIGO).","volume":"69","author":"Moe","year":"2006","journal-title":"Kidney Int"},{"key":"B3-20230813","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1001\/jama.2011.308","article-title":"Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis.","volume":"305","author":"Palmer","year":"2011","journal-title":"JAMA"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2215\/CJN.04650512","article-title":"The case for routine parathyroid hormone monitoring.","volume":"8","author":"Sprague","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"B5-20230813","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/j.1523-1755.2005.67139.x","article-title":"Achieving NKF-K\/DOQI bone metabolism and disease treatment goals with cinacalcet HCl.","volume":"67","author":"Moe","year":"2005","journal-title":"Kidney 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Transplant"},{"key":"B9-20230813","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/ndt\/gfs080","article-title":"Contribution of calcium, phosphorus and 25-hydroxyvitamin D to the excessive severity of secondary hyperparathyroidism in African-Americans with CKD.","volume":"27","author":"Ennis","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"B10-20230813","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/ki.2008.4","article-title":"Prevalence and severity of disordered mineral metabolism in blacks with chronic kidney disease.","volume":"73","author":"Guti\u00e9rrez","year":"2008","journal-title":"Kidney Int"},{"key":"B11-20230813","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1053\/ajkd.2002.35694","article-title":"The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients.","volume":"40","author":"Ert\u00fcrk","year":"2002","journal-title":"Am J Kidney 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concentrations.","volume":"353","author":"Cole","year":"1999","journal-title":"Lancet"},{"key":"B15-20230813","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1530\/eje.0.1450421","article-title":"Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism.","volume":"145","author":"Miedlich","year":"2001","journal-title":"Eur J Endocrinol"},{"key":"B16-20230813","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S0895-7061(99)00285-X","article-title":"Molecular variations in the calcium-sensing receptor in relation to sodium balance and presence of hypertension in blacks and whites.","volume":"13","author":"Pratt","year":"2000","journal-title":"Am J Hypertens"},{"key":"B17-20230813","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses.","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J 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calcium-sensing receptor, CaSR, in fetal development.","volume":"27","author":"Riccardi","year":"2013","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B31-20230813","doi-asserted-by":"crossref","first-page":"E841","DOI":"10.1152\/ajpendo.00599.2011","article-title":"The calcium-sensing receptor complements parathyroid hormone-induced bone turnover in discrete skeletal compartments in mice.","volume":"302","author":"Xue","year":"2012","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B32-20230813","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/jbmr.2089","article-title":"A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD.","volume":"29","author":"Moe","year":"2014","journal-title":"J Bone Miner Res"},{"key":"B33-20230813","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/CIRCULATIONAHA.114.013876","article-title":"Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial.","volume":"132","author":"Moe","year":"2015","journal-title":"Circulation"}],"container-title":["Clinical Journal of the American Society of 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