The vitamin D receptor gene FokI polymorphism: functional impact on the immune system

Eur J Immunol. 2007 Feb;37(2):395-405. doi: 10.1002/eji.200636043.


1Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) has important effects on the growth and function of multiple cell types. These pleiotropic effects of 1,25(OH)2D3 are mediated through binding to the vitamin D receptor (VDR). Several polymorphisms of the human VDR gene have been identified, with the FokI polymorphism resulting in VDR proteins with different structures, a long f-VDR or a shorter F-VDR. The aim of this study was to investigate the functional consequences of the FokI polymorphism in immune cells. In transfection experiments, the presence of the shorter F-VDR resulted in higher NF-kappaB- and NFAT-driven transcription as well as higher IL-12p40 promoter-driven transcription. Marginal differences were observed for AP-1-driven transcription, and no differential effects were observed for transactivation of a classical vitamin D-responsive element. Concordantly, in human monocytes and dendritic cells with a homozygous short FF VDR genotype, expression of IL-12 (mRNA and protein) was higher than in cells with a long ff VDR genotype. Additionally, lymphocytes with a short FF VDR genotype proliferated more strongly in response to phytohemagglutinin. Together, these data provide the first evidence that the VDR FokI polymorphism affects immune cell behavior, with a more active immune system for the short F-VDR, thus possibly playing a role in immune-mediated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-12 Subunit p40 / immunology
  • Interleukin-12 Subunit p40 / metabolism
  • Jurkat Cells
  • Mice
  • Middle Aged
  • Monocytes / immunology
  • Polymorphism, Genetic / immunology*
  • Promoter Regions, Genetic
  • Protein Isoforms / genetics
  • RNA, Messenger / analysis
  • Receptors, Calcitriol / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection


  • Interleukin-12 Subunit p40
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Calcitriol
  • Transcription Factors