Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene

Giuseppe Vezzoli, Alfredo Scillitani, Sabrina Corbetta, Annalisa Terranegra, Elena Dogliotti, Vito Guarnieri, Teresa Arcidiacono, Lorenza Macrina, Alessandra Mingione, Caterina Brasacchio, Cristina Eller-Vainicher, Daniele Cusi, Anna Spada, David E C Cole, Geoffrey N. Hendy, Donatella Spotti, Laura Soldati

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aims: Two single-nucleotide polymorphisms (SNPs) at the calcium-sensing receptor (CASR) gene were previously associated with kidney stones in patients with primary hyperparathyroidism (PHPT): rs1501899, likely associated with a decrease in CASR expression, and Arg990Gly, causing a gain of CASR function. To evaluate the interaction of these two SNPs in the stone risk, we tested the association of stones with the genotype at both SNPs in PHPT patients and the association of rs1501899 with CASR expression as messenger RNA (mRNA) in human kidney samples.

Methods and results: Two hundred and ninety-six PHPT patients were genotyped at the rs1501899 and Arg990Gly SNPs. Minor allele frequency at tested SNPs was higher in PHPT stone formers relative to non-stone forming patients. PHPT patients carrying one or two copies of the minor allele at both rs1501899 and Arg990Gly (n = 16) had the maximal risk of stones (odds ratio, OR 8.3) and higher serum ionized calcium compared with homozygous patients for the wild-type allele at both SNPs. CASR expression as mRNA was measured by real time polymerase chain reaction (PCR) in normal kidney medulla samples from 109 subjects. CASR mRNA was significantly lower in medulla samples from homozygotes for the minor allele at rs1501899 than in subjects with other genotypes.

Conclusions: We conclude that the simultaneous presence of the minor allele at rs1501899 and Arg990Gly may amplify the kidney stone risk in PHPT patients, despite their apparently opposite effects on CASR function in the kidney.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalJournal of Nephrology
Volume28
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Calcium-Sensing Receptors
Nephrolithiasis
Primary Hyperparathyroidism
Single Nucleotide Polymorphism
Genes
Alleles
Kidney Calculi
Messenger RNA
Genotype
Kidney Medulla
Kidney
Homozygote
Gene Frequency
Real-Time Polymerase Chain Reaction
Odds Ratio
Calcium
Serum

Keywords

  • Calcium
  • Calcium-sensing receptor
  • Hyperparathyroidism
  • Kidney stones

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene. / Vezzoli, Giuseppe; Scillitani, Alfredo; Corbetta, Sabrina; Terranegra, Annalisa; Dogliotti, Elena; Guarnieri, Vito; Arcidiacono, Teresa; Macrina, Lorenza; Mingione, Alessandra; Brasacchio, Caterina; Eller-Vainicher, Cristina; Cusi, Daniele; Spada, Anna; Cole, David E C; Hendy, Geoffrey N.; Spotti, Donatella; Soldati, Laura.

In: Journal of Nephrology, Vol. 28, No. 1, 2014, p. 67-72.

Research output: Contribution to journalArticle

Vezzoli, G, Scillitani, A, Corbetta, S, Terranegra, A, Dogliotti, E, Guarnieri, V, Arcidiacono, T, Macrina, L, Mingione, A, Brasacchio, C, Eller-Vainicher, C, Cusi, D, Spada, A, Cole, DEC, Hendy, GN, Spotti, D & Soldati, L 2014, 'Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene', Journal of Nephrology, vol. 28, no. 1, pp. 67-72. https://doi.org/10.1007/s40620-014-0106-8
Vezzoli, Giuseppe ; Scillitani, Alfredo ; Corbetta, Sabrina ; Terranegra, Annalisa ; Dogliotti, Elena ; Guarnieri, Vito ; Arcidiacono, Teresa ; Macrina, Lorenza ; Mingione, Alessandra ; Brasacchio, Caterina ; Eller-Vainicher, Cristina ; Cusi, Daniele ; Spada, Anna ; Cole, David E C ; Hendy, Geoffrey N. ; Spotti, Donatella ; Soldati, Laura. / Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene. In: Journal of Nephrology. 2014 ; Vol. 28, No. 1. pp. 67-72.
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abstract = "Aims: Two single-nucleotide polymorphisms (SNPs) at the calcium-sensing receptor (CASR) gene were previously associated with kidney stones in patients with primary hyperparathyroidism (PHPT): rs1501899, likely associated with a decrease in CASR expression, and Arg990Gly, causing a gain of CASR function. To evaluate the interaction of these two SNPs in the stone risk, we tested the association of stones with the genotype at both SNPs in PHPT patients and the association of rs1501899 with CASR expression as messenger RNA (mRNA) in human kidney samples.Methods and results: Two hundred and ninety-six PHPT patients were genotyped at the rs1501899 and Arg990Gly SNPs. Minor allele frequency at tested SNPs was higher in PHPT stone formers relative to non-stone forming patients. PHPT patients carrying one or two copies of the minor allele at both rs1501899 and Arg990Gly (n = 16) had the maximal risk of stones (odds ratio, OR 8.3) and higher serum ionized calcium compared with homozygous patients for the wild-type allele at both SNPs. CASR expression as mRNA was measured by real time polymerase chain reaction (PCR) in normal kidney medulla samples from 109 subjects. CASR mRNA was significantly lower in medulla samples from homozygotes for the minor allele at rs1501899 than in subjects with other genotypes.Conclusions: We conclude that the simultaneous presence of the minor allele at rs1501899 and Arg990Gly may amplify the kidney stone risk in PHPT patients, despite their apparently opposite effects on CASR function in the kidney.",
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T1 - Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene

AU - Vezzoli, Giuseppe

AU - Scillitani, Alfredo

AU - Corbetta, Sabrina

AU - Terranegra, Annalisa

AU - Dogliotti, Elena

AU - Guarnieri, Vito

AU - Arcidiacono, Teresa

AU - Macrina, Lorenza

AU - Mingione, Alessandra

AU - Brasacchio, Caterina

AU - Eller-Vainicher, Cristina

AU - Cusi, Daniele

AU - Spada, Anna

AU - Cole, David E C

AU - Hendy, Geoffrey N.

AU - Spotti, Donatella

AU - Soldati, Laura

PY - 2014

Y1 - 2014

N2 - Aims: Two single-nucleotide polymorphisms (SNPs) at the calcium-sensing receptor (CASR) gene were previously associated with kidney stones in patients with primary hyperparathyroidism (PHPT): rs1501899, likely associated with a decrease in CASR expression, and Arg990Gly, causing a gain of CASR function. To evaluate the interaction of these two SNPs in the stone risk, we tested the association of stones with the genotype at both SNPs in PHPT patients and the association of rs1501899 with CASR expression as messenger RNA (mRNA) in human kidney samples.Methods and results: Two hundred and ninety-six PHPT patients were genotyped at the rs1501899 and Arg990Gly SNPs. Minor allele frequency at tested SNPs was higher in PHPT stone formers relative to non-stone forming patients. PHPT patients carrying one or two copies of the minor allele at both rs1501899 and Arg990Gly (n = 16) had the maximal risk of stones (odds ratio, OR 8.3) and higher serum ionized calcium compared with homozygous patients for the wild-type allele at both SNPs. CASR expression as mRNA was measured by real time polymerase chain reaction (PCR) in normal kidney medulla samples from 109 subjects. CASR mRNA was significantly lower in medulla samples from homozygotes for the minor allele at rs1501899 than in subjects with other genotypes.Conclusions: We conclude that the simultaneous presence of the minor allele at rs1501899 and Arg990Gly may amplify the kidney stone risk in PHPT patients, despite their apparently opposite effects on CASR function in the kidney.

AB - Aims: Two single-nucleotide polymorphisms (SNPs) at the calcium-sensing receptor (CASR) gene were previously associated with kidney stones in patients with primary hyperparathyroidism (PHPT): rs1501899, likely associated with a decrease in CASR expression, and Arg990Gly, causing a gain of CASR function. To evaluate the interaction of these two SNPs in the stone risk, we tested the association of stones with the genotype at both SNPs in PHPT patients and the association of rs1501899 with CASR expression as messenger RNA (mRNA) in human kidney samples.Methods and results: Two hundred and ninety-six PHPT patients were genotyped at the rs1501899 and Arg990Gly SNPs. Minor allele frequency at tested SNPs was higher in PHPT stone formers relative to non-stone forming patients. PHPT patients carrying one or two copies of the minor allele at both rs1501899 and Arg990Gly (n = 16) had the maximal risk of stones (odds ratio, OR 8.3) and higher serum ionized calcium compared with homozygous patients for the wild-type allele at both SNPs. CASR expression as mRNA was measured by real time polymerase chain reaction (PCR) in normal kidney medulla samples from 109 subjects. CASR mRNA was significantly lower in medulla samples from homozygotes for the minor allele at rs1501899 than in subjects with other genotypes.Conclusions: We conclude that the simultaneous presence of the minor allele at rs1501899 and Arg990Gly may amplify the kidney stone risk in PHPT patients, despite their apparently opposite effects on CASR function in the kidney.

KW - Calcium

KW - Calcium-sensing receptor

KW - Hyperparathyroidism

KW - Kidney stones

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