![]() ![]() However, the CASR R990G polymorphism, which was investigated in small groups (n ≤ 20) of patients with primary HPT related to type 1 multiple endocrine neoplasia and in patients with sHPT, was not associated with the efficacy profile of cinacalcet 19. Cinacalcet was also effective with a heterozygous mutation (R185Q, CGA > CAA) in exon 4 of CASR 18. These studies showed that CASR R990G influences the response to calcimimetics in patients with sHPT with an odds ratio of 2.6 12. Studies of the association between CASR and the response to treatment with the calcimimetic agent cinacalcet included CASR R990G. The glands of patients with the GG genotype were more sensitive to extracellular changes in ionized Ca 10. In 2002, the CASR R990G polymorphism was shown to influence the response of the parathyroid glands to changes in extracellular ionized Ca in HD patients. 17 reported that CASR polymorphisms of G990R and intron 5 were closely associated with the magnitude of PTH secretion and/or PTH degradation as well as the clinical severity in primary HPT patients. 9 demonstrated the association of CASR alleles (codon 990) with PTH secretion in HD patients. The CASR A986S (rs1801725) polymorphism was also associated with coronary artery disease (CAD), myocardial infarction (MI), all-cause mortality, and cardiovascular mortality in non-dialyzed subjects 13.ĬaSR in parathyroid cells is sensitive to ionized Ca concentration and regulates PTH secretion 14. Serum PTH concentrations and other features of sHPT 9, 10, as well as treatment with cinacalcet 11, 12, seem to be associated with CASR (OMIM +601199) polymorphisms. Calcimimetics, allosteric activators of CaSR, provide an effective means of reducing parathyroid hormone (PTH) secretion in such patients 8. CaSR expression is decreased in human uremic parathyroid glands to nearly 60% of normal expressionα 7. Mineral bone disorders, including secondary hyperparathyroidism (sHPT), are closely associated with cardiovascular complications and are the main cause of morbidity and mortality in haemodialysis (HD) subjects 6. It was also demonstrated that the minor allele in rs6776158 may predispose to Ca stones by decreasing transcriptional activity of the CASR promoter 1 and CaSR expression in kidney tubules 4. It was suggested that the appearance of the binding site for the octamer-binding transcription factor 1 (Oct-1) proximal to CASR promoters may downregulate calcium-sensing receptor (CaSR) expression in subjects with the minor allele in rs7652589 or rs1501899 5. Risk calcium-sensing receptor gene ( CASR) genotypes in rs1042636, rs7652589, rs1501899, and rs6776158 were proposed as markers that could identify patients prone to developing Ca nephrolithiasis 3, 4. Struvite stones (in humans, a mixture of struvite and carbonate-apatite 1) account for a further 42.2% of cases 2. According to computational analysis, potential binding sites for GLI3, AHR and TP53 are removed by the A allele, whereas binding sites for SOX18 and TP63 are created.Ĭalcium (Ca) stones contribute to nephrolithiasis-related end-stage renal disease (ESRD), which requires renal replacement therapy (RRT) in 26.7% of cases. The A allele is associated with reduced CaSR transcript level in peripheral blood mononuclear cells. ![]() The AA genotype is associated with more severe sHPT (higher Ca and PTH concentrations). This study shows that the A allele of rs7652589 is a risk allele for nephrolithiasis-related ESRD. Healthy individuals (n = 918) were controls. We aimed to determine the associations of rs7652589 with nephrolithiasis-related ESRD, Ca, P, ALP, PTH, response to treatment with cinacalcet, prevalence of coronary artery disease, and all-cause/cardiovascular mortality in HD patients (n = 1162). We hypothesized that CASR rs7652589 variants may also influence CaSR in end stage renal disease (ESRD). The minor allele at this polymorphism modifies the binding sites of transcription factors and CaSR expression. ![]() Polymorphism in CaSR gene ( CASR) influences Ca-related parameters, however it was not shown in HD patients for CASR rs7652589. Calcimimetics, activators of the calcium-sensing receptor (CaSR), provide an effective means of reducing parathyroid hormone (PTH) secretion in sHPT. Nephrolithiasis, secondary hyperparathyroidism (sHPT), and cardiovascular complications are associated with disturbances in Ca handling and contribute to morbidity/mortality during haemodialysis (HD). ![]()
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