Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1, 25-dihydroxyvitamin D3

Clin Endocrinol (Oxf). 2000 Feb;52(2):211-6. doi: 10.1046/j.1365-2265.2000.00909.x.


Objective: In the vitamin D receptor (VDR) gene a BsmI restriction fragment length polymorphism (RFLP) in intron 8 and a translational start-site polymorphism, identified as a FokI RFLP, have been described. Crucial for a proper interpretation of these polymorphisms in association studies is the knowledge whether they have direct consequences for 1,25-(OH)2D3 action at cellular level. The present study was designed to assess functional significance of the FokI and BsmI VDR gene polymorphisms in peripheral blood mononuclear cells (PBMC) with a natural occurring VDR genotype for cell growth inhibition by 1,25-(OH)2D3.

Design: PBMC of women were isolated, VDR genotyped and in vitro inhibition by 1,25-(OH)2D3 of Phytohemagglutinin (PHA)-stimulated growth of PBMC was examined in relation to VDR genotype.

Results: PHA-stimulated growth and maximal growth inhibition were independent of VDR genotype. However, the FF genotype had a significant lower ED50 than the Ff genotype corresponding to an allele dose effect of 0.32 nM per f allele copy (P = 0.0036). For BsmI genotypes no differences in ED50 were observed.

Conclusion: The present study demonstrates for the first time in cells with a natural VDR genotype a direct functional consequence of the VDR gene translational start-site polymorphism for the action of 1,25-(OH)2D3. Especially under conditions of vitamin D insufficiency these findings might have clinical implications.

MeSH terms

  • Aged
  • Alleles
  • Analysis of Variance
  • Calcitriol / pharmacology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Depression, Chemical
  • Female
  • Gene Dosage
  • Genotype
  • Humans
  • Leukocytes, Mononuclear / cytology*
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*


  • Receptors, Calcitriol
  • Calcitriol