Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome

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Norheim, Katrine BraekkeStavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway. (författare)

Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome

Artikel/kapitelEngelska2016

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2016-03-10
Oxford University Press (OUP),2016
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LIBRIS-ID:oai:DiVA.org:uu-299502
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-299502URI
https://doi.org/10.1093/rheumatology/kew008DOI

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Språk:engelska
Sammanfattning på:engelska

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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.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reumatologi och inflammation hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Rheumatology and Autoimmunity hsv//eng
primary Sjogren's syndrome
epigenetics
DNA methylation
fatigue

Biuppslag (personer, institutioner, konferenser, titlar ...)

Imgenberg-Kreuz, JulianaUppsala universitet,Molekylär medicin(Swepub:uu)julim920 (författare)
Jonsdottir, KristinStavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway. (författare)
Janssen, Emiel A. M.Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway. (författare)
Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin(Swepub:uu)anncsyva (författare)
Sandling, Johanna K.Uppsala universitet,Reumatologi(Swepub:uu)josan062 (författare)
Nordmark, GunnelUppsala universitet,Reumatologi(Swepub:uu)gunnnord (författare)
Omdal, RoaldStavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway. (författare)
Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway.Molekylär medicin (creator_code:org_t)

Sammanhörande titlar

Ingår i:Rheumatology: Oxford University Press (OUP)55:6, s. 1074-10821462-03241462-0332

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