title: Vitamin D status and gene transcription in immune cells.
abstract: 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).
  
  
  CONCLUSIONS
  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'.
authors: Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Germany. yasmin_moran@gmx.de
authors: Y
authors: Y
authors: Morán-Auth
authors: M
authors: M
authors: Penna-Martinez
authors: F
authors: F
authors: Shoghi
authors: E
authors: E
authors: Ramos-Lopez
authors: K
authors: K
authors: Badenhoop
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D014644:Genetic Variation / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D018167:Receptors, Calcitriol / Q000235:genetics; D014807:Vitamin D / Q000235:genetics* / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase