Polymorphisms at the regulatory regions of the CASR gene influence stone risk in primary hyperparathyroidism. |
Authors: |
Vezzoli, G Scillitani, A Corbetta, S Terranegra, A Dogliotti, E Guarnieri, V Arcidiacono, T Paloschi, V Rainone, F Eller-Vainicher, C Borghi, L Nouvenne, A Guerra, A Meschi, T Allegri, F Cusi, D Spada, A Cole, DE Hendy, GN Spotti, D Soldati, L
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Citation: |
Vezzoli G, etal., Eur J Endocrinol. 2011 Mar;164(3):421-7. doi: 10.1530/EJE-10-0915. Epub 2010 Dec 23. |
RGD ID: |
7205447 |
Pubmed: |
PMID:21183554 (View Abstract at PubMed) |
DOI: |
DOI:10.1530/EJE-10-0915 (Journal Full-text) |
BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms (SNPs) of the calcium-sensing receptor (CASR) gene at the regulatory region were associated with idiopathic calcium nephrolithiasis. To confirm their association with nephrolithiasis, we tested patients with primary hyperparathyroidism (PHPT). DESIGN: A genotype-phenotype association study. METHODS: In all, 332 PHPT patients and 453 healthy controls were genotyped for the rs7652589 (G>A) and rs1501899 (G>A) SNPs sited in the noncoding regulatory region of the CASR gene. Allele, haplotype, and diplotype distribution were compared between PHPT patients and controls, and in stone forming and stone-free PHPT patients. RESULTS: The allele frequency at rs7652589 and rs1501899 SNPs was similar in PHPT patients and controls. The A minor alleles at these two SNPs were more frequent in stone forming (n=157) than in stone-free (n=175) PHPT patients (rs7652589: 36.9 vs 27.1%, P=0.007; rs1501899: 37.1 vs 26.4%, P=0.003). Accordingly, homozygous or heterozygous PHPT patients for the AA haplotype (n=174, AA/AA or AA/GG diplotype) had an increased stone risk (odds ratio 1.83, 95% confidence interval 1.2-2.9, P=0.008). Furthermore, these PHPT patients had higher serum concentrations of ionized calcium and parathyroid hormone (1.50 +/- 0.015 mmol/l and 183 +/- 12.2 pg/ml) than patients with the GG/GG diplotype (n=145, 1.47 +/- 0.011 mmol/l (P=0.04) and 150 +/- 11.4 pg/ml (P=0.049)). Using a logistic regression model, the increase in stone risk in PHPT patients was predicted by AA/AA or AA/GG diplotype, the highest tertile of serum ionized calcium values and the lowest tertile of age. CONCLUSIONS: Polymorphisms located in the regulatory region of the CASR gene may increase susceptibility of the PHPT patients to kidney stone production.
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