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dc.contributor.authorVukić, Maja
dc.contributor.authorNeme, Antonio
dc.contributor.authorSeuter, Sabine
dc.contributor.authorSaksa, Noora
dc.contributor.authorde Mello, Vanessa D. F.
dc.contributor.authorNurmi, Tarja
dc.contributor.authorUusitupa, Matti
dc.contributor.authorTuomainen, Tomi-Pekka
dc.date.accessioned2016-06-03T12:09:31Z
dc.date.available2016-06-03T12:09:31Z
dc.date.issued2015-04-13
dc.identifierdoi:10.1371/journal.pone.0124339
dc.identifier.citationVukić M, Neme A, Seuter S, Saksa N, de Mello VDF, Nurmi T, et al. (2015) Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells. PLoS ONE 10(4): e0124339. doi:10.1371/journal.pone.0124339fi_FI
dc.identifier.issn1932-6203
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/39
dc.descriptionArticle
dc.description.abstractVitamin 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.fi_FI
dc.language.isoenfi_FI
dc.publisherPublic Library of Science (PLoS)fi_FI
dc.relation.ispartofseriesPLOS ONE
dc.relation.urihttp://dx.doi.org/10.1371/journal.pone.0124339
dc.rightsCC BY 4.0 https://creativecommons.org/licenses/by/4.0/
dc.subjectVitaminsfi_FI
dc.subjectVitamin Dfi_FI
dc.subjectGene expressionfi_FI
dc.subjectGenetic networksfi_FI
dc.subjectGlucose tolerance testsfi_FI
dc.subjectNetwork analysisfi_FI
dc.subjectBiomarkersfi_FI
dc.subjectDNA transcriptionfi_FI
dc.titleRelevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cellsfi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionPublisher Version
dc.contributor.departmentTerveystieteiden tiedekunta
uef.solecris.id32304743
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Vukić et al
dc.relation.doi10.1371/journal.pone.0124339
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.issn1932-6203
dc.relation.issue4
dc.relation.volume10
dc.rights.accesslevelopenAccess


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