title: R990G polymorphism of the calcium-sensing receptor and renal calcium excretion in patients with primary hyperparathyroidism.
abstract: BACKGROUND
  Primary hyperparathyroidism (PHPT) shows a great variability in clinical course and severity. Data concerning the association between polymorphic variants of the gene encoding the calcium-sensing receptor (CaSR) and clinical characteristics of PHPT are not conclusive.
  
  
  OBJECTIVE
  To evaluate the frequency of three polymorphisms; A986S, R990G, and Q1011E of CaSR in patients with PHPT and to correlate the genotypes with clinical and biochemical parameters.
  
  
  METHODS
  The study included 94 consecutive unrelated patients referred to our Departments for PHPT diagnosis and management between 2000 and 2005 and 137 age and sex-matched healthy subjects. Patients and controls were genotyped according to standard procedures. Due to the rarity of 990G allele, homozygous and heterozygous subjects were grouped in R/G+G/G set. All PHPT patients were studied for calcium metabolism parameters and renal and bone complications.
  
  
  RESULTS
  The proportion of CaSRvariants was similar in PHPT patients and controls. In PHPT patients, only R990G polymorphism was associated with disease parameters; in comparison with R/R, R/G+G/G patients showed lower mean serum parathyroid hormone (PTH) and phosphate levels (139.9 +/- 62.2 vs 199.9 +/- 136.3 pg/ml, P < 0.05 and 0.69 +/- 0.12 vs 0.81 +/- 0.18 mmol/l, P = 0.031 respectively), higher mean 24-h urine calcium concentration and calcium excretion (9.05 +/- 2.05 vs 6.77 +/- 4.31 mmol/24 h, P = 0.012 and 67 +/- 20 vs 51 +/- 26 mumol/l GF, P = 0.039), and increased prevalence of nephrolithiasis (90.0 vs 44.2%, P = 0.007).
  
  
  CONCLUSIONS
  The study showed that patients with PHPT, bearing the 990G allele, had lower serum PTH levels and higher urinary calcium excretion in comparison with the other genotype, suggesting an increased sensitivityof the variant receptor to extracellular calcium. Since this variant was associated with increased occurrence of nephrolithiasis, analysis of this polymorphism might help to predict renal complication of the disease.
authors.affiliation: Unità Operativa di Endocrinologia e Diabetologia, Department of Medical-Surgical Sciences, University of Milan, Policlinico San Donato IRCCS, San Donato M.se, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Corbetta
authors.forename: C
authors.initials: C
authors.lastname: Eller-Vainicher
authors.forename: M
authors.initials: M
authors.lastname: Filopanti
authors.forename: P
authors.initials: P
authors.lastname: Saeli
authors.forename: G
authors.initials: G
authors.lastname: Vezzoli
authors.forename: T
authors.initials: T
authors.lastname: Arcidiacono
authors.forename: P
authors.initials: P
authors.lastname: Loli
authors.forename: M L
authors.initials: ML
authors.lastname: Syren
authors.forename: L
authors.initials: L
authors.lastname: Soldati
authors.forename: P
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: A
authors.initials: A
authors.lastname: Spada
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D002118:Calcium / Q000652:urine*; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics* / Q000652:urine; D006973:Hypertension / Q000235:genetics; D008297:Male; D053040:Nephrolithiasis / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics; D011110:Polymorphism, Genetic; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium