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'.
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'.
Authors: Kristine C Olson; Paige M Kulling Larkin; Rossana Signorelli; Cait E Hamele; Thomas L Olson; Mark R Conaway; David J Feith; Thomas P Loughran Journal: Cytokine Date: 2018-11-17 Impact factor: 3.861
Authors: Maggie Ham; Maria S Longhi; Conor Lahiff; Adam Cheifetz; Simon Robson; Alan C Moss Journal: Inflamm Bowel Dis Date: 2014-05 Impact factor: 5.325