Vitamin D status and gene transcription in immune cells

J Steroid Biochem Mol Biol. 2013 Jul;136:83-5. doi: 10.1016/j.jsbmb.2013.02.005. Epub 2013 Feb 13.


Background: Vitamin D is a modulator of the immune system. Its insufficiency has been implicated in type 1 diabetes (T1D) and studies showed significant associations with polymorphisms of vitamin D genes. Aim of the study was to investigate whether gene expression in immune cells, vitamin D status and genetic variants are correlated in healthy controls (HC).

Methods: From 23 HC monocytes (Mo), T-helper cells (Th) and natural killer cells (NK) were isolated. In all immune cells gene expression of vitamin D receptor (VDR), 25-vitamin-D-hydroxylase (CYP2R1) and 25-hydroxyvitamin-D3-1a-hydroxylase (CYP27B1) were measured by Taqman assay. Furthermore, CYP2R1 (rs10741657), CYP27B1 (rs10877012) and the VDR-FokI (rs10735810) polymorphisms in HC were genotyped. Finally, 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plasma levels in HC were measured by radioimmunoassay.

Results: All studied immune cells showed a significantly different gene expression of CYP2R1 and CYP27B1 (p=1×10(-6), respectively). When stratifying the HC according to vitamin D deficiency and vitamin D sufficiency, within the 25(OH)D3 deficient group significantly lower 1,25(OH)2D3 plasma levels (p=0.02) in HC and a significant down-regulation of the VDR expression only in Mo were observed (p=0.04). Furthermore, a significant correlation between CYP2R1 gene transcription and 1,25(OH)2D3 plasma levels in Th cells was found (p=0.04). No associations between the gene expression levels and the investigated polymorphism in all different immune cells were detected. However, vitamin D deficiency in combination with the "AC" CYP27B1 genotype appeared to inhibit the CYP27B1 expression in NK cells (p=0.03).

Conclusion: both 25(OH)D3 deficiency and low 1,25(OH)2D3 levels appear to interact with its system gene transcription illustrating the relevance for targeted vitamin D therapy. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Adult
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cytochrome P450 Family 2
  • Female
  • Gene Expression Regulation / immunology*
  • Genetic Variation / immunology
  • Humans
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Receptors, Calcitriol / genetics
  • Vitamin D / genetics*
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / immunology
  • Vitamin D Deficiency / metabolism


  • Receptors, Calcitriol
  • Vitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase