title: Association of polymorphic alleles of the calcium-sensing receptor gene with the clinical severity of primary hyperparathyroidism.
abstract: OBJECTIVE
  Primary hyperparathyroidism (pHPT) is a heterogeneous disease in its clinical course and severity. Previous studies have suggested an association between the clinical severity of pHPT and the genotypes of vitamin D receptor, oestrogen receptors and PTH molecules. The Ca-sensing receptor (CaR) is activated by an extracellular calcium ion and controls PTH secretion, and thus polymorphisms of CaR might be associated with the magnitude of PTH secretion and the clinical severity of pHPT. In this study, we examined the relationship between CaR polymorphisms and biochemical markers in pHPT patients.
  
  
  METHODS
  We analysed 105 Japanese pHPT patients (85 females and 20 males; mean age 55.6 +/- 14.0 years). We determined the CaR genotypes of G990R and intron 5 polymorphisms with genomic DNA extracted from peripheral lymphocytes. The intron 5 polymorphism was defined as T/T, T/C and C/C.
  
  
  RESULTS
  In the G990R polymorphism, serum levels of both intact PTH and alkaline phosphatase (ALP) were significantly higher and the serum level of phosphorus was significantly lower in the RR group than in the GG group. In the intron 5 polymorphism, the T/T group showed significantly lower serum levels of intact PTH and Ca. Furthermore, patients with both the codon 990 RR and the intron 5 C allele (the RRC(+) group) had significantly higher serum levels of intact PTH and ALP than did the other patients.
  
  
  CONCLUSIONS
  The present study is the first to show that CaR polymorphisms of G990R and intron 5 were closely associated with the magnitude of PTH secretion and/or PTH degradation as well as the clinical severity in pHPT patients.
authors.affiliation: Third Division, Department of Medicine, Kobe University School of Medicine, Chuo-ku, Kobe, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamauchi
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Yano
authors.forename: M
authors.initials: M
authors.lastname: Kanzawa
authors.forename: A
authors.initials: A
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Chihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000483:Alleles; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011110:Polymorphism, Genetic; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D010758:Phosphorus; D000469:Alkaline Phosphatase; D002118:Calcium