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Genome-wide DNA met...
Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes
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- Imgenberg-Kreuz, Juliana (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Sandling, Johanna K. (author)
- Uppsala universitet,Reumatologi,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Almlöf, Jonas Carlsson (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Nordlund, Jessica (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Signér, Linnea (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Norheim, Katrine Braekke (author)
- Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway
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- Omdal, Roald (author)
- Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Eloranta, Maija-Leena (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Syvänen, Ann-Christine (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Nordmark, Gunnel (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2016-02-08
- 2016
- English.
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:11, s. 2029-2036
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Abstract
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- OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
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- art (subject category)
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Imgenberg-Kreuz, ...
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Sandling, Johann ...
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Almlöf, Jonas Ca ...
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Nordlund, Jessic ...
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Signér, Linnea
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Norheim, Katrine ...
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show more...
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Omdal, Roald
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Rönnblom, Lars
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Eloranta, Maija- ...
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Syvänen, Ann-Chr ...
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Nordmark, Gunnel
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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Uppsala University