Introduction: Both environmental and genetic factors may contribute to determine Primary hyperparathyroidism (PHPT) phenotypes. Calcium-sensing-receptor (CASR) gene variants could explain genetic susceptibility to PHPT and its clinical course’s heterogeneity. Research studies investigated associations among three single nucleotides polymorphisms (A986S - R990G - Q1011E) and clinical features of PHPT; however, they’ve often produced conflicting conclusions. Aims: to evaluate the prevalence of SNPs in patients with sporadic PHPT and their impact on its clinical course, biochemistry and histological features. Material & methods: 106 patients underwent clinical and anamnestic examination (focusing on main PHPT complications), biochemical sampling of blood and urine, and genetic analysis (for CASR-gene polymorphisms); 68 of them underwent parathyroidectomy, therefore histology was also available. Results: Patients included 83 women and 23 men; mean age at diagnosis was 54.5 years (range 21-84 years). 55 patients had CASR-gene polymorphisms, while 51 were wild-type. The prevalence data of polymorphisms align with existing literature for the Caucasian population, with the majority (31%) of patients carrying the A986S variant. No association was found between the A986S, R990G and Q1011E polymorphisms of the CASR gene and increased levels of ionized calcium, nor other blood parameters of phospho-calcium metabolism. However, 24-hour urinary calcium values are higher in subjects carrying the polymorphism compared to wild-type subjects (p=0.0185, Mann Whitney test), especially in those over 50 (p=0.030) and in patients with the A986S polymorphism. The presence of hypercalciuria can predict CASR gene mutation (Odds Ratio = 2.76, p=0.003). No significant prevalence of SNPs in younger age groups was documented. Regarding PHPT complications, the association between the R990G variant and renal calculosis was not confirmed, nor was any association found with bone involvement. Among patients with histological diagnosis, no statistically significant association was unequivocal found between polymorphisms and more aggressive histological variants. Conclusions: Our study did not confirm the biochemical associations described in the literature, even considering the different sample selection among various studies. In patients with PHPT, the presence of CASR gene polymorphism is associated with hypercalciuria, which in turn is predictive of a positive genetic test. The presence of a mutation does not seem to influence the age of onset and clinical phenotype but may be correlated with a different histological diagnosis. In the future, genetic analysis could be indicated in selected cases to clarify the clinical profile of the patient.

Introduction: Both environmental and genetic factors may contribute to determine Primary hyperparathyroidism (PHPT) phenotypes. Calcium-sensing-receptor (CASR) gene variants could explain genetic susceptibility to PHPT and its clinical course’s heterogeneity. Research studies investigated associations among three single nucleotides polymorphisms (A986S - R990G - Q1011E) and clinical features of PHPT; however, they’ve often produced conflicting conclusions. Aims: to evaluate the prevalence of SNPs in patients with sporadic PHPT and their impact on its clinical course, biochemistry and histological features. Material & methods: 106 patients underwent clinical and anamnestic examination (focusing on main PHPT complications), biochemical sampling of blood and urine, and genetic analysis (for CASR-gene polymorphisms); 68 of them underwent parathyroidectomy, therefore histology was also available. Results: Patients included 83 women and 23 men; mean age at diagnosis was 54.5 years (range 21-84 years). 55 patients had CASR-gene polymorphisms, while 51 were wild-type. The prevalence data of polymorphisms align with existing literature for the Caucasian population, with the majority (31%) of patients carrying the A986S variant. No association was found between the A986S, R990G and Q1011E polymorphisms of the CASR gene and increased levels of ionized calcium, nor other blood parameters of phospho-calcium metabolism. However, 24-hour urinary calcium values are higher in subjects carrying the polymorphism compared to wild-type subjects (p=0.0185, Mann Whitney test), especially in those over 50 (p=0.030) and in patients with the A986S polymorphism. The presence of hypercalciuria can predict CASR gene mutation (Odds Ratio = 2.76, p=0.003). No significant prevalence of SNPs in younger age groups was documented. Regarding PHPT complications, the association between the R990G variant and renal calculosis was not confirmed, nor was any association found with bone involvement. Among patients with histological diagnosis, no statistically significant association was unequivocal found between polymorphisms and more aggressive histological variants. Conclusions: Our study did not confirm the biochemical associations described in the literature, even considering the different sample selection among various studies. In patients with PHPT, the presence of CASR gene polymorphism is associated with hypercalciuria, which in turn is predictive of a positive genetic test. The presence of a mutation does not seem to influence the age of onset and clinical phenotype but may be correlated with a different histological diagnosis. In the future, genetic analysis could be indicated in selected cases to clarify the clinical profile of the patient.

“Analysis of CASR gene polymorphisms in a cohort of italian patients affected by primary hyperparathyroidism”

CANNITO, MICHELE
2022/2023

Abstract

Introduction: Both environmental and genetic factors may contribute to determine Primary hyperparathyroidism (PHPT) phenotypes. Calcium-sensing-receptor (CASR) gene variants could explain genetic susceptibility to PHPT and its clinical course’s heterogeneity. Research studies investigated associations among three single nucleotides polymorphisms (A986S - R990G - Q1011E) and clinical features of PHPT; however, they’ve often produced conflicting conclusions. Aims: to evaluate the prevalence of SNPs in patients with sporadic PHPT and their impact on its clinical course, biochemistry and histological features. Material & methods: 106 patients underwent clinical and anamnestic examination (focusing on main PHPT complications), biochemical sampling of blood and urine, and genetic analysis (for CASR-gene polymorphisms); 68 of them underwent parathyroidectomy, therefore histology was also available. Results: Patients included 83 women and 23 men; mean age at diagnosis was 54.5 years (range 21-84 years). 55 patients had CASR-gene polymorphisms, while 51 were wild-type. The prevalence data of polymorphisms align with existing literature for the Caucasian population, with the majority (31%) of patients carrying the A986S variant. No association was found between the A986S, R990G and Q1011E polymorphisms of the CASR gene and increased levels of ionized calcium, nor other blood parameters of phospho-calcium metabolism. However, 24-hour urinary calcium values are higher in subjects carrying the polymorphism compared to wild-type subjects (p=0.0185, Mann Whitney test), especially in those over 50 (p=0.030) and in patients with the A986S polymorphism. The presence of hypercalciuria can predict CASR gene mutation (Odds Ratio = 2.76, p=0.003). No significant prevalence of SNPs in younger age groups was documented. Regarding PHPT complications, the association between the R990G variant and renal calculosis was not confirmed, nor was any association found with bone involvement. Among patients with histological diagnosis, no statistically significant association was unequivocal found between polymorphisms and more aggressive histological variants. Conclusions: Our study did not confirm the biochemical associations described in the literature, even considering the different sample selection among various studies. In patients with PHPT, the presence of CASR gene polymorphism is associated with hypercalciuria, which in turn is predictive of a positive genetic test. The presence of a mutation does not seem to influence the age of onset and clinical phenotype but may be correlated with a different histological diagnosis. In the future, genetic analysis could be indicated in selected cases to clarify the clinical profile of the patient.
2022
“Analysis of CASR gene polymorphisms in a cohort of italian patients affected by primary hyperparathyroidism”
Introduction: Both environmental and genetic factors may contribute to determine Primary hyperparathyroidism (PHPT) phenotypes. Calcium-sensing-receptor (CASR) gene variants could explain genetic susceptibility to PHPT and its clinical course’s heterogeneity. Research studies investigated associations among three single nucleotides polymorphisms (A986S - R990G - Q1011E) and clinical features of PHPT; however, they’ve often produced conflicting conclusions. Aims: to evaluate the prevalence of SNPs in patients with sporadic PHPT and their impact on its clinical course, biochemistry and histological features. Material & methods: 106 patients underwent clinical and anamnestic examination (focusing on main PHPT complications), biochemical sampling of blood and urine, and genetic analysis (for CASR-gene polymorphisms); 68 of them underwent parathyroidectomy, therefore histology was also available. Results: Patients included 83 women and 23 men; mean age at diagnosis was 54.5 years (range 21-84 years). 55 patients had CASR-gene polymorphisms, while 51 were wild-type. The prevalence data of polymorphisms align with existing literature for the Caucasian population, with the majority (31%) of patients carrying the A986S variant. No association was found between the A986S, R990G and Q1011E polymorphisms of the CASR gene and increased levels of ionized calcium, nor other blood parameters of phospho-calcium metabolism. However, 24-hour urinary calcium values are higher in subjects carrying the polymorphism compared to wild-type subjects (p=0.0185, Mann Whitney test), especially in those over 50 (p=0.030) and in patients with the A986S polymorphism. The presence of hypercalciuria can predict CASR gene mutation (Odds Ratio = 2.76, p=0.003). No significant prevalence of SNPs in younger age groups was documented. Regarding PHPT complications, the association between the R990G variant and renal calculosis was not confirmed, nor was any association found with bone involvement. Among patients with histological diagnosis, no statistically significant association was unequivocal found between polymorphisms and more aggressive histological variants. Conclusions: Our study did not confirm the biochemical associations described in the literature, even considering the different sample selection among various studies. In patients with PHPT, the presence of CASR gene polymorphism is associated with hypercalciuria, which in turn is predictive of a positive genetic test. The presence of a mutation does not seem to influence the age of onset and clinical phenotype but may be correlated with a different histological diagnosis. In the future, genetic analysis could be indicated in selected cases to clarify the clinical profile of the patient.
iperparatiroidismo
CASR
polimorfismo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/81449