Plasma parathyroid hormone, phosphatemia and vitamin D receptor genotype: are they interrelated?

It is not clear how the rate of bone mineral loss and vitamin D receptor (VDR) Bsml polymorphism in hemodialysed patients are related. We therefore analysed the relationships between indices of calcium-phosphate metabolism in respect to VDR genotype in 180 hemodialysed patients. We measured plasma concentrations of calcium, phosphate, iPTH, 1,25(OH)2D3 and activity of the bone fraction of alkaline phosphatase on the day before dialysis. VDR genotype BB, Bb and bb were found in 39, 84 and 57 patients, respectively. The allele frequency was B 0.45 and b 0.55. Subjects with BB genotype had insignificantly higher plasma levels of phosphate, iPTH and activity of the bone fraction of alkaline phosphatase, but significantly lower (p<0.02) concentrations of 1,25(OH)2D3 [iP (mmol/l): 2.05+/-0.09, 1.98+/-0.06, 1.93+/-0.06; iPTH (pg/ml): 257+/-50, 229+/-24, 219+/-30; AP(BF) (nmol/l/s): 515+/-45, 477+/-27, 457+/-34; 1,25(OH)2D3 (pg/ml): 23.4+/-1.5, 26.2+/-1.0, 29.3+/-1.3, for BB, Bb and bb respectively]. The strongest significant correlation between phosphatemia and iPTH was in the BB subgroup (r=0.343). Moreover, only in this subgroup did phosphatemia significantly contribute to the increase in iPTH, assessed by multiple regression analysis. In conclusion, it seems likely that BB VDR genotype in HD patients contributes to the severity of secondary hyperparathyroidism by a mechanism involving phosphatemia.