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Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome
Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway..
Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway..
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2016 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 55, no 6, 1074-1082 p.Article in journal (Refereed) PublishedText
Abstract [en]

Objective. Chronic fatigue is a common, disabling and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary SS (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods. Forty-eight pSS patients with high (n = 24) or low (n = 24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. After quality control, a total of 383 358 Cytosine-phosphate-Guanine (CpG) sites remained for further analysis. Age, sex and differential cell count estimates were included as covariates in the association model. A false discovery rate-corrected P < 0.05 was considered significant, and a cut-off of 3% average difference in methylation levels between high- and low-fatigue patients was applied. Results. A total of 251 differentially methylated CpG sites were associated with fatigue. The CpG site with the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene. The most distinct hypermethylation was observed at a CpG site annotated to the lymphotoxin alpha gene. Functional pathway analysis of genes with differently methylated CpG sites in subjects with high vs low fatigue revealed enrichment in several pathways associated with innate and adaptive immunity. Conclusion. Some genes involved in regulation of the immune system and in inflammation are differently methylated in pSS patients with high vs low fatigue. These findings point to functional networks that may underlie fatigue. Epigenetic changes could constitute a fatigue-regulating mechanism in pSS.

Place, publisher, year, edition, pages
2016. Vol. 55, no 6, 1074-1082 p.
Keyword [en]
primary Sjogren's syndrome, epigenetics, DNA methylation, fatigue
National Category
Rheumatology and Autoimmunity
URN: urn:nbn:se:uu:diva-299502DOI: 10.1093/rheumatology/kew008ISI: 000377432200015OAI: oai:DiVA.org:uu-299502DiVA: diva2:949694
Available from: 2016-07-22 Created: 2016-07-22 Last updated: 2016-07-22Bibliographically approved

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Imgenberg-Kreuz, JulianaSyvänen, Ann-ChristineSandling, Johanna K.Nordmark, Gunnel
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