Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients

Giuseppe Vezzoli, Annalisa Tanini, Luigi Ferrucci, Laura Soldati, Cristiana Bianchin, Francesco Franceschelli, Cecilia Malentacchi, Berardino Porfirio, Donatella Adamo, Alberto Falchetti, Annalisa Terranegra, Daniele Cusi, Giuseppe Bianchi, Maria Luisa Brandi

Research output: Contribution to journalArticle

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Abstract

Calcium-sensing receptor (CaSR) is a plasma membrane protein that regulates tubular reabsorption of Ca. To establish its role in idiopathic hypercalciuria, the association of urinary Ca excretion with the polymorphisms of CASR gene has been studied in healthy subjects and in hypercalciuric and normocalciuric Ca stone formers. CASR exon 7 single nucleotide polymorphisms (SNP), G/T at codon 986, G/A at codon 990, and C/G at codon 1011, were evaluated by PCR amplification and direct sequencing in 97 normocalciuric stone formers, 134 hypercalciuric stone formers, and 101 normocalciuric healthy controls. Four haplotypes were defined on the basis of CASR gene SNP: haplotype 1 was characterized by the most frequent sequence; haplotypes 2, 3, or 4 by the presence of a single polymorphic variant at codon 986, 990, or 1011, respectively. The relative risk of hypercalciuria was calculated with multinomial logistic regression and was significantly increased only in individuals carrying haplotype 3 (Odds ratio, 13.0 [95% confidence interval, 1.7 to 99.4]). Accordingly, Ca excretion was higher in subjects bearing haplotype 3, whereas those bearing haplotype 2 showed a slight increase of plasma Ca concentration. Multiple regression analysis showed that haplotype 3 explained 4.1% of the total variance of Ca excretion and 12.6% of the variance explained by the variables considered in the study. In conclusion, CASR gene could be a component of the complex genetic background regulating Ca excretion. Arg990Gly polymorphism could facilitate activation of CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria.

Original languageEnglish
Pages (from-to)2517-2523
Number of pages7
JournalJournal of the American Society of Nephrology
Volume13
Issue number10
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

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Calcium-Sensing Receptors
Haplotypes
Calcium
Hypercalciuria
Codon
Genes
Single Nucleotide Polymorphism
Blood Proteins
Exons
Healthy Volunteers
Membrane Proteins
Logistic Models
Odds Ratio
Regression Analysis
Cell Membrane
Confidence Intervals
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Nephrology

Cite this

Vezzoli, G., Tanini, A., Ferrucci, L., Soldati, L., Bianchin, C., Franceschelli, F., ... Brandi, M. L. (2002). Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. Journal of the American Society of Nephrology, 13(10), 2517-2523. https://doi.org/10.1097/01.ASN.0000030077.72157.D2

Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. / Vezzoli, Giuseppe; Tanini, Annalisa; Ferrucci, Luigi; Soldati, Laura; Bianchin, Cristiana; Franceschelli, Francesco; Malentacchi, Cecilia; Porfirio, Berardino; Adamo, Donatella; Falchetti, Alberto; Terranegra, Annalisa; Cusi, Daniele; Bianchi, Giuseppe; Brandi, Maria Luisa.

In: Journal of the American Society of Nephrology, Vol. 13, No. 10, 01.10.2002, p. 2517-2523.

Research output: Contribution to journalArticle

Vezzoli, G, Tanini, A, Ferrucci, L, Soldati, L, Bianchin, C, Franceschelli, F, Malentacchi, C, Porfirio, B, Adamo, D, Falchetti, A, Terranegra, A, Cusi, D, Bianchi, G & Brandi, ML 2002, 'Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients', Journal of the American Society of Nephrology, vol. 13, no. 10, pp. 2517-2523. https://doi.org/10.1097/01.ASN.0000030077.72157.D2
Vezzoli, Giuseppe ; Tanini, Annalisa ; Ferrucci, Luigi ; Soldati, Laura ; Bianchin, Cristiana ; Franceschelli, Francesco ; Malentacchi, Cecilia ; Porfirio, Berardino ; Adamo, Donatella ; Falchetti, Alberto ; Terranegra, Annalisa ; Cusi, Daniele ; Bianchi, Giuseppe ; Brandi, Maria Luisa. / Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. In: Journal of the American Society of Nephrology. 2002 ; Vol. 13, No. 10. pp. 2517-2523.
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abstract = "Calcium-sensing receptor (CaSR) is a plasma membrane protein that regulates tubular reabsorption of Ca. To establish its role in idiopathic hypercalciuria, the association of urinary Ca excretion with the polymorphisms of CASR gene has been studied in healthy subjects and in hypercalciuric and normocalciuric Ca stone formers. CASR exon 7 single nucleotide polymorphisms (SNP), G/T at codon 986, G/A at codon 990, and C/G at codon 1011, were evaluated by PCR amplification and direct sequencing in 97 normocalciuric stone formers, 134 hypercalciuric stone formers, and 101 normocalciuric healthy controls. Four haplotypes were defined on the basis of CASR gene SNP: haplotype 1 was characterized by the most frequent sequence; haplotypes 2, 3, or 4 by the presence of a single polymorphic variant at codon 986, 990, or 1011, respectively. The relative risk of hypercalciuria was calculated with multinomial logistic regression and was significantly increased only in individuals carrying haplotype 3 (Odds ratio, 13.0 [95{\%} confidence interval, 1.7 to 99.4]). Accordingly, Ca excretion was higher in subjects bearing haplotype 3, whereas those bearing haplotype 2 showed a slight increase of plasma Ca concentration. Multiple regression analysis showed that haplotype 3 explained 4.1{\%} of the total variance of Ca excretion and 12.6{\%} of the variance explained by the variables considered in the study. In conclusion, CASR gene could be a component of the complex genetic background regulating Ca excretion. Arg990Gly polymorphism could facilitate activation of CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria.",
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AU - Franceschelli, Francesco

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AU - Terranegra, Annalisa

AU - Cusi, Daniele

AU - Bianchi, Giuseppe

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