Influence of Bsml vitamin D receptor gene polymorphism on the response to a single bolus of calcitrol in hemodialysis patients

Clin Nephrol. 2001 Aug;56(2):111-6.

Abstract

Aims: BsmI polymorphism of the vitamin D receptor gene has been linked to hyperparathyroidism severity and calcitriol levels. The aim of this study was to analyze the response to a single bolus of calcitriol in hemodialysis patients with the BB and bb genotype.

Patients: Twenty homozygous BsmI hemodialysis patients (9 BB and 11 bb).

Methods: Hyperparathyroidism was assessed comparing basal PTH levels, and in 17 patients, also measuring the inhibition with hypercalcemia. Patients were given a bolus of calcitriol and PTH in absolute terms and in percentages relative to the baseline values at 24, 48 and 72 hours after the bolus were measured. All biochemical parameters were compared between genotypes with univariant ANOVA and additionally, PTH relative values were compared with general factorial analysis of variance, adjusting for calcium and phosphorus. Means were also compared within each genotype between consecutive determinations with non-parametric Wilcoxon analysis, using each patient as his/her own control. The response to calcitriol was also assessed by the area under the curve for each patient and was subsequently compared between genotypes.

Results: There were no differences on hyperparathyroidism severity between the groups. The BB genotype showed a better response than bb to calcitriol 72 hours after the bolus (percentage relative to basal PTH value: BB: 63%, bb: 88.6%, p = 0.03; BB vs bb with univariant ANOVA). When general factorial analysis of variance was applied, adjusting for serum calcium and phosphorus, genotype showed a significant influence on the response to calcitriol at 72 hours (p = 0.04). When each patient was used as his/her own control, the BB genotype showed a significant decrease in PTH levels at 48 and 72 hours (p = 0.00 baseline vs 48 h, and p = 0.01 baseline vs 72h) whereas the bb did not.

Conclusions: BsmI polymorphism of the VDR gene induces differences on the response to a single bolus of calcitriol independently of calcium and phosphorus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Calcitriol / pharmacology*
  • Calcium / blood
  • Calcium Channel Agonists / pharmacology*
  • Deoxyribonucleases, Type II Site-Specific
  • Genotype
  • Humans
  • Hyperparathyroidism / blood
  • Hyperparathyroidism / genetics*
  • Parathyroid Glands / drug effects*
  • Parathyroid Hormone / blood*
  • Phosphorus / blood
  • Polymorphism, Genetic
  • Receptors, Calcitriol / genetics*
  • Renal Dialysis
  • Time Factors

Substances

  • Calcium Channel Agonists
  • Parathyroid Hormone
  • Receptors, Calcitriol
  • Phosphorus
  • endodeoxyribonuclease BsmI
  • Deoxyribonucleases, Type II Site-Specific
  • Calcitriol
  • Calcium