Polymorphisms at the regulatory regions of the CASR gene influence stone risk in primary hyperparathyroidism

Giuseppe Vezzoli, Alfredo Scillitani, Sabrina Corbetta, Annalisa Terranegra, Elena Dogliotti, Vito Guarnieri, Teresa Arcidiacono, Vera Paloschi, Francesco Rainone, Cristina Eller-Vainicher, Loris Borghi, Antonio Nouvenne, Angela Guerra, Tiziana Meschi, Franca Allegri, Daniele Cusi, Anna Spada, David E C Cole, Geoffrey N. Hendy, Donatella SpottiLaura Soldati

Research output: Contribution to journalArticlepeer-review


Background and objective: Single nucleotide polymorphisms (SNPs) of the calcium-sensing receptor (CASR) gene at the regulatory region were associated with idiopathic calcium nephrolithiasis. To confirm their association with nephrolithiasis, we tested patients with primary hyperparathyroidism (PHPT). Design: A genotype-phenotype association study. Methods: In all, 332 PHPT patients and 453 healthy controls were genotyped for the rs7652589 (G>A) and rs1501899 (G>A) SNPs sited in the noncoding regulatory region of the CASR gene. Allele, haplotype, and diplotype distribution were compared between PHPT patients and controls, and in stone forming and stone-free PHPT patients. Results: The allele frequency at rs7652589 and rs1501899 SNPs was similar in PHPT patients and controls. The A minor alleles at these two SNPs were more frequent in stone forming (n=157) than in stone-free (n=175) PHPT patients (rs7652589: 36.9 vs 27.1%, P=0.007; rs1501899: 37.1 vs 26.4%, P=0.003). Accordingly, homozygous or heterozygous PHPT patients for the AA haplotype (n=174, AA/AA or AA/GG diplotype) had an increased stone risk (odds ratio 1.83, 95% confidence interval 1.2-2.9, P=0.008). Furthermore, these PHPT patients had higher serum concentrations of ionized calcium and parathyroid hormone (1.50±0.015 mmol/l and 183±12.2 pg/ml) than patients with the GG/GG diplotype (n=145, 1.47±0.011 mmol/l (P=0.04) and 150±11.4 pg/ml (P=0.049)). Using a logistic regression model, the increase in stone risk in PHPT patients was predicted by AA/AA or AA/GG diplotype, the highest tertile of serum ionized calcium values and the lowest tertile of age. Conclusions: Polymorphisms located in the regulatory region of the CASR gene may increase susceptibility of the PHPT patients to kidney stone production.

Original languageEnglish
Pages (from-to)421-427
Number of pages7
JournalEuropean Journal of Endocrinology
Issue number3
Publication statusPublished - Mar 1 2011

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)


Dive into the research topics of 'Polymorphisms at the regulatory regions of the CASR gene influence stone risk in primary hyperparathyroidism'. Together they form a unique fingerprint.

Cite this