Endocrine Abstracts

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that regulates extracellular calcium concentration. The CaSR is also implicated in the pathogenesis of non-calcium disorders such as vascular calcification and diabetes, which are leading causes of cardiovascular disease. Common CaSR single nucleotide polymorphisms (SNPs) have been demonstrated to be determinants of calcium metabolism. The aim of this study was to investigate whether CaSR SNPs may influence vascular calcification in renal transplant recipients, a patient group in which cardiovascular disease is the major cause of death. Three coding region polymorphisms (Ala986Ser, Arg990Gly, Gln1011Glu) and three CaSR promoter polymorphism (rs115759455, rs7652589, rs150189) were analyzed in 285 renal transplant recipients that had undergone radiological assessment of aortic medial and coronary artery intimal calcification, vessel wall stiffness, and measurement of calcification risk factors including blood pressure, renal function, and indices of calcium and glucose homeostasis. Univariate and multivariate analysis for associations was performed by regression analysis. The frequencies of the Ala986Ser, Arg990Gly, Gln1011Glu, rs115759455, rs7652589 and rs1501899 alleles in the transplant recipients were 0.88/0.12, 0.94/0.06, 0.97/0.03, 0.95/0.05, 0.63/0.37 and 0.64/0.36 respectively. The CaSR SNP allelic frequencies obeyed the Hardy-Weinberg equilibrium and did not significantly differ from previously reported population cohorts. A significant negative association was revealed between rs7652589 and levels of coronary artery calcifications (odds ratio (OR)=0.83, P<0.05). Moreover, significant positive associations were demonstrated between rs115759455 and serum phosphate concentrations (OR=1.14, P<0.01), and Ala986Ser and plasma glucose concentrations (OR=1.17, P<0.05). Thus, the rs7652589 CaSR SNP was associated with a beneficial effect on intimal calcification within the coronary vessels. Whereas, the rs115759455 and Ala986Ser SNPs were associated with increased levels of serum phosphate and glucose, which are promoters of arterial medial calcification. Our findings indicate novel associations between common CaSR polymorphisms and vascular calcification and glucose homeostasis.

Declaration of funding: This work was supported by a Mary Curie Early stage researcher fellowship.