title: Vitamin D receptor polymorphisms correlate to parathyroid cell function in primary hyperparathyroidism.
abstract: Calcitriol acts via its receptor (VDR) and inhibits PTH secretion and parathyroid cell proliferation. Increased prevalence of the polymorphic VDR alleles b, a, and T has been demonstrated in sporadic primary hyperparathyroidism. Sixty-two patients with primary hyperparathyroidism due to parathyroid adenoma (mean age, 69.5 +/- 1.4 yr) were genotyped for these VDR polymorphisms. Dispersed cells of the adenomas were exposed to increasing concentrations of extracellular Ca2+ and analyzed for PTH release and cytoplasmic Ca2+ concentrations. Ca2+-mediated PTH inhibition exhibited higher ED50 and less suppression in the cells of patients who were homozygous for the b, a, and T alleles (P < 0.05-0.10). When analyzing haplotypes, the patients with baT demonstrated a ED50 of 1.81 +/- 0.15 vs. 1.29 +/- 0.10 for BAt (P < 0.05). As VDR alleles were unrelated to parathyroid intracellular Ca2+, influences of polymorphic VDR alleles on PTH secretion seem to involve mechanisms other than the Ca2+-sensing protein of the parathyroid cell surface.
authors.affiliation: Department of Surgery, Uppsala University Hospital, Sweden. Tobias.Carling@kirurgi.uu.se
authors.forename: T
authors.initials: T
authors.lastname: Carling
authors.forename: P
authors.initials: P
authors.lastname: Ridefelt
authors.forename: P
authors.initials: P
authors.lastname: Hellman
authors.forename: J
authors.initials: J
authors.lastname: Rastad
authors.forename: G
authors.initials: G
authors.lastname: Akerström
mesh_terms: D000236:Adenoma / Q000150:complications / Q000473:pathology; D000368:Aged; D000483:Alleles; D002118:Calcium / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006961:Hyperparathyroidism / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D010280:Parathyroid Glands / Q000473:pathology / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors; D010282:Parathyroid Neoplasms / Q000150:complications / Q000473:pathology; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D002118:Calcium