Endocrine Abstracts

The calcium receptor (CASR) serves as one of the main regulators of the calcium homeostasis. CASR is expressed in among other tissues parathyroid chief cells and kidney tubule cells. It has been hypothesized that CASR gene variations are responsible for low circulating calcium levels together with hypercalciuria and thereby increased risk of kidney stones. The CASR gene polymorphism A986S has been shown associated to elevated serum calcium levels in vivo. On the opposite R990G has been shown associated to low serum calcium levels.

Aim: Are the polymorphisms A986S and R990G overrepresented in hypercalciuria patients with low normal serum calcium levels.

Method: The CASR gene was sequenced in 109 Italian out-patient Caucasians suffering hypercalciuria (calcium excretion >4 mg calcium/day). The patients had low normal serum calcium values and serum PTH within the normal range. All had normal kidney function.

Results: Sixty-eight of 109 patients (62%) showed at least one single-nucleotide polymorphism (SNP). Up to 4 SNP’s were found in each patient, all well characterised. Of these 37 patients (28%) presented A986S, 12 patients (13%) the R990G polymorphism.

Discussion: The observed A986S and R990G distribution corresponds to the frequency and genotype shown in the ancestry population of Northern and Western European.

Conclusion: A986S or the R990G polymorphism does not explain hypercalciuria and low normal serum calcium in this cohort.