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.
Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene / G. Vezzoli, A. Scillitani, S. Corbetta, A. Terranegra, E. Dogliotti, V. Guarnieri, T. Arcidiacono, L. Macrina, A. Mingione, C. Brasacchio, C. Eller-Vainicher, D. Cusi, A. Spada, D. Cole, G. Hendy, D. Spotti, L. Soldati. - In: JN. JOURNAL OF NEPHROLOGY. - ISSN 1121-8428. - 28:1(2015 Feb), pp. 67-72.
|Titolo:||Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene|
SOLDATI, LAURA (Ultimo)
|Parole Chiave:||Hyperparathyroidism; Calcium; Kidney stones; Calcium-sensing receptor|
|Settore Scientifico Disciplinare:||Settore MED/49 - Scienze Tecniche Dietetiche Applicate|
Settore MED/14 - Nefrologia
Settore MED/13 - Endocrinologia
|Data di pubblicazione:||feb-2015|
|Data ahead of print / Data di stampa:||16-mag-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s40620-014-0106-8|
|Appare nelle tipologie:||01 - Articolo su periodico|