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. 2025 Aug 19;16(8):974.
doi: 10.3390/genes16080974.

CaSR Gene Polymorphisms and PHPT Phenotypes: What Else Can We Learn? A Single-Center Experience on a Cohort of Italian Patients

Michele Cannito  1   2 , Giacomo Voltan  1   2 , Giulia Carraro  2 , Michela Ferrarese  1   2 , Giacomo Contini  1   2 , Carlo Mogno  1   2 , Loris Bertazza  1   2 , Susi Barollo  1   2 , Francesca Torresan  3   4 , Maurizio Iacobone  3   4 , Caterina Mian  1   2 , Valentina Camozzi  1   2
Affiliations

CaSR Gene Polymorphisms and PHPT Phenotypes: What Else Can We Learn? A Single-Center Experience on a Cohort of Italian Patients

Michele Cannito et al. Genes (Basel). .

Abstract

Purpose: This study investigates the role of CASR gene polymorphisms (A986S, R990G, Q1011E) in PHPT genetic susceptibility and its clinical variability. The aim is to evaluate the prevalence of these polymorphisms in patients with sporadic PHPT and their impact on clinical course, biochemistry, and histological features. Methods: 106 patients underwent clinical and anamnestic evaluations, focusing on major PHPT complications, as well as biochemical analyses of blood and urine. Genetic testing was conducted for CASR gene polymorphisms. Histological data were available for 68 patients who underwent parathyroidectomy. Results: The sample included 83 women and 23 men; mean age at diagnosis was 54.5 years. 55 patients carried CASR gene polymorphisms, while 51 were wild-type. Prevalence rates of polymorphisms were consistent with data for the Caucasian population, with A986S being the most common (31%). No significant associations were found between polymorphisms and increased levels of ionized calcium or other blood phospho-calcium metabolism parameters. However, 24-h urinary calcium levels were higher in patients with polymorphisms (p = 0.0185), particularly in those older than 50 years (p = 0.030) and with the A986S variant. Hypercalciuria was predictive of CASR polymorphism presence (OR = 2.76, p = 0.003). No significant association with PHPT complications, such as renal calculi or bone involvement, was confirmed. Histological data revealed no clear links between polymorphisms and more aggressive variants. Conclusions: CASR gene polymorphisms are associated with hypercalciuria but do not significantly influence age of onset or clinical phenotype in PHPT. Genetic analysis may be useful in selected cases to better understand individual clinical profiles.

Keywords: Calcium-Sensing Receptor (CASR); Primary Hyperparathyroidism (PHPT); Single Nucleotide Polymorphism (SNPs); hypercalciuria.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Number of subjects in the various phases of the study.
Figure 2
Figure 2
Urinary calcium values comparison with box-and-whiskers plot.
Figure 3
Figure 3
Urinary calcium values comparison with box-and-whiskers plot, according to patients’ age.
Figure 4
Figure 4
Logistic regression analysis: the presence of hypercalciuria is predictive for CASR gene SNPs presence.
Figure 5
Figure 5
Statistical analysis of prevalence according to histological diagnosis.
See this image and copyright information in PMC

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