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 language | English |
|---|---|
| Pages (from-to) | 67-72 |
| Number of pages | 6 |
| Journal | Journal of Nephrology |
| Volume | 28 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Calcium
- Calcium-sensing receptor
- Hyperparathyroidism
- Kidney stones
ASJC Scopus subject areas
- Nephrology
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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84922569951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922569951&partnerID=8YFLogxK
U2 - 10.1007/s40620-014-0106-8
DO - 10.1007/s40620-014-0106-8
M3 - Article
C2 - 24832896
AN - SCOPUS:84922569951
VL - 28
SP - 67
EP - 72
JO - Journal of Nephrology
JF - Journal of Nephrology
SN - 1121-8428
IS - 1
ER -