dc.date.accessioned | 2020-04-11T18:53:56Z | |
dc.date.available | 2020-04-11T18:53:56Z | |
dc.date.created | 2013-09-06T12:45:09Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Handel, Adam E Sandve, Geir Kjetil Disanto, Giulio Berlanga-Taylor, Antonio Gallone, Anna Hanwell, Heather EC Drabløs, Finn Giovannoni, Gavin Ebers, Georg C Ramagopalan, Sreeram V . Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease. BMC Medicine. 2013, 11(163) | |
dc.identifier.uri | http://hdl.handle.net/10852/74478 | |
dc.description.abstract | Background
Vitamin D insufficiency has been implicated in autoimmunity. ChIP-seq experiments using immune cell lines have shown that vitamin D receptor (VDR) binding sites are enriched near regions of the genome associated with autoimmune diseases. We aimed to investigate VDR binding in primary CD4+ cells from healthy volunteers.
Methods
We extracted CD4+ cells from nine healthy volunteers. Each sample underwent VDR ChIP-seq. Our results were analyzed in relation to published ChIP-seq and RNA-seq data in the Genomic HyperBrowser. We used MEMEChIP for de novo motif discovery. 25-Hydroxyvitamin D levels were measured using liquid chromatography–tandem mass spectrometry and samples were divided into vitamin D sufficient (25(OH)D ≥75 nmol/L) and insufficient/deficient (25(OH)D <75 nmol/L) groups.
Results
We found that the amount of VDR binding is correlated with the serum level of 25-hydroxyvitamin D (r = 0.92, P= 0.0005). In vivo VDR binding sites are enriched for autoimmune disease associated loci, especially when 25-hydroxyvitamin D levels (25(OH)D) were sufficient (25(OH)D ≥75: 3.13-fold, P<0.0001; 25(OH)D <75: 2.76-fold, P<0.0001; 25(OH)D ≥75 enrichment versus 25(OH)D <75 enrichment: P= 0.0002). VDR binding was also enriched near genes associated specifically with T-regulatory and T-helper cells in the 25(OH)D ≥75 group. MEME ChIP did not identify any VDR-like motifs underlying our VDR ChIP-seq peaks.
Conclusion
Our results show a direct correlation between in vivo 25-hydroxyvitamin D levels and the number of VDR binding sites, although our sample size is relatively small. Our study further implicates VDR binding as important in gene-environment interactions underlying the development of autoimmunity and provides a biological rationale for 25-hydroxyvitamin D sufficiency being based at 75 nmol/L. Our results also suggest that VDR binding in response to physiological levels of vitamin D occurs predominantly in a VDR motif-independent manner. | |
dc.language | EN | |
dc.rights | Attribution 2.0 Generic | |
dc.rights.uri | https://creativecommons.org/licenses/by/2.0/ | |
dc.title | Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease | |
dc.type | Journal article | |
dc.creator.author | Handel, Adam E | |
dc.creator.author | Sandve, Geir Kjetil | |
dc.creator.author | Disanto, Giulio | |
dc.creator.author | Berlanga-Taylor, Antonio | |
dc.creator.author | Gallone, Anna | |
dc.creator.author | Hanwell, Heather EC | |
dc.creator.author | Drabløs, Finn | |
dc.creator.author | Giovannoni, Gavin | |
dc.creator.author | Ebers, Georg C | |
dc.creator.author | Ramagopalan, Sreeram V | |
cristin.unitcode | 185,15,5,35 | |
cristin.unitname | Forskningsgruppen for biomedisinsk informatikk | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1047502 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=BMC Medicine&rft.volume=11&rft.spage=&rft.date=2013 | |
dc.identifier.jtitle | BMC Medicine | |
dc.identifier.volume | 11 | |
dc.identifier.issue | 1 | |
dc.identifier.pagecount | 11 | |
dc.identifier.doi | https://doi.org/10.1186/1741-7015-11-163 | |
dc.identifier.urn | URN:NBN:no-77583 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1741-7015 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/74478/2/Handel.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 163 | |