RGD Reference Report - Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor. - Rat Genome Database

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Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor.

Authors: Scillitani, Alfredo  Guarnieri, Vito  Battista, Claudia  De Geronimo, Simona  Muscarella, Lucia Anna  Chiodini, Iacopo  Cignarelli, Mauro  Minisola, Salvatore  Bertoldo, Francesco  Francucci, Cristiano M  Malavolta, Nazzarena  Piovesan, Alessandro  Mascia, Maria Lucia  Muscarella, Silvana  Hendy, Geoffrey N  D'Agruma, Leonardo  Cole, David E C 
Citation: Scillitani A, etal., J Clin Endocrinol Metab. 2007 Jan;92(1):277-83. doi: 10.1210/jc.2006-0857. Epub 2006 Oct 3.
RGD ID: 13464331
Pubmed: (View Article at PubMed) PMID:17018660
DOI: Full-text: DOI:10.1210/jc.2006-0857

INTRODUCTION: Three single-nucleotide polymorphisms in the calcium-sensing receptor gene (CASR) encoding the missense substitutions A986S, R990G, and Q1011E have been associated with normal variation in extracellular calcium homeostasis, both individually and in haplotype combination. The aim of this study was to examine haplotype associations in primary hyperparathyroidism (PHPT).
PATIENTS AND METHODS: Patients with sporadic PHPT (n = 237) were recruited from endocrine clinics and healthy controls (n = 433) from a blood donor clinic, and levels of serum calcium, albumin, and PTH were measured. In PHPT patients, urinary calcium/creatinine clearances and bone mineral density at spine and femoral neck were measured and the presence of kidney stones and vertebral fractures identified. The CASR single-nucleotide polymorphisms were haplotyped by allele-specific sequencing.
RESULTS: Four haplotypes (ARQ, SRQ, AGQ, and ARE) of eight were observed, in keeping with significant linkage disequilibrium, but haplotype frequencies did not show significant Hardy-Weinberg disequilibrium. The SRQ haplotype was more common in PHPT (125 of 474 alleles) than in controls (170 of 866 alleles, P = 0.006) and showed a significant (P = 0.006) gene-dosage effect. There was no significant association between haplotype and bone mineral density or fractures, but association with kidney stones was significant (P = 0.0007). In the stone-forming subgroup, the SRQ haplotype was underrepresented and AGQ overrepresented. Patients bearing the AGQ haplotype had an odds ratio of 3.8 (95% confidence interval, 1.30-11.3) for presentation with renal stones compared with the rest.
CONCLUSION: Our data indicate that the CASR SRQ haplotype is significantly associated with PHPT in our population. Within the PHPT patient population, the AGQ haplotype is significantly associated with kidney stones.


Disease Annotations    

Phenotype Annotations    

Human Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Casr  (calcium-sensing receptor)

Genes (Mus musculus)
Casr  (calcium-sensing receptor)

Genes (Homo sapiens)
CASR  (calcium sensing receptor)

Additional Information