title: Relevance of vitamin D receptor target genes for monitoring the vitamin D responsiveness of primary human cells.
abstract: Vitamin D3 has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D3 to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using samples from a 5-month vitamin D3 intervention study (VitDmet), we recently reported that the expression of 12 VDR target genes in peripheral blood mononuclear cells (PBMCs) as well as 12 biochemical and clinical parameters of the study participants are significantly triggered by vitamin D3. In this study, we performed a more focused selection of further 12 VDR target genes and demonstrated that changes of their mRNA expression in PBMCs of VitDmet subjects significantly correlate with alterations of 25-hydroxyvitamin D3 serum levels. Network and self-organizing map analysis of these datasets together with that of the other 24 parameters was followed by relevance calculations and identified changes in parathyroid hormone serum levels and the expression of the newly selected genes STS, BCL6, ITGAM, LRRC25, LPGAT1 and TREM1 as well as of the previously reported genes DUSP10 and CD14 as the most relevant parameters for describing vitamin D responsiveness in vivo. Moreover, parameter relevance ranking allowed the segregation of study subjects into high and low responders. Due to the long intervention period the vitamin D response was not too prominent on the level of transcriptional activation. Therefore, we performed in the separate VitDbol trial a short-term but high dose stimulation with a vitamin D3 bolus. In PBMCs of VitDbol subjects we observed direct transcriptional effects on the selected VDR target genes, such as an up to 2.1-fold increase already one day after supplementation onset. In conclusion, both long-term and short-term vitamin D3 supplementation studies allow monitoring the vitamin D responsiveness of human individuals and represent new types of human in vivo vitamin D3 investigations.
authors: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Maja
authors: M
authors: Vukić
authors: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Antonio
authors: A
authors: Neme
authors: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Sabine
authors: S
authors: Seuter
authors: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Noora
authors: N
authors: Saksa
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors: Vanessa D F
authors: VD
authors: de Mello
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors: Tarja
authors: T
authors: Nurmi
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors: Matti
authors: M
authors: Uusitupa
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors: Tomi-Pekka
authors: TP
authors: Tuomainen
authors: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors: Jyrki K
authors: JK
authors: Virtanen
authors: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Carsten
authors: C
authors: Carlberg
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014815:Vitamins; C118756:dihydroxy-vitamin D3; D014807:Vitamin D