Epigenome-Wide DNA Methylation Patterns Associated with Fatigue in Primary Sjögren’s Syndrome

Katrine B Norheim¹, Juliana Imgenberg-Kreuz², Kristin Jonsdottir³, Emiel Janssen⁴, Ann-Christine Syvänen², Johanna K Sandling², Gunnel Nordmark⁵ and Roald Omdal⁶, ¹Dept of Internal Medicine, Clinical immunology Unit, Stavanger, Norway, ²Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, ³Dept. of Pathology, Stavanger University Hospital, Stavanger, Norway, ⁴Dept. of Pathology, Stavanger university Hospital, Stavanger, Norway, ⁵Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, ⁶Department of internal medicine, Clinical Immunology unit, Stavanger, Norway

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: epigenetics and fatigue, Sjogren's syndrome

Session Information

Date: Monday, November 9, 2015

Title: Genetics, Genomics and Proteomics Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Chronic fatigue is a common, often disabling, and poorly understood phenomenon of many diseases. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, which is a prominent feature of primary Sjögren’s syndrome (pSS), a chronic autoimmune disease. The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS.

Methods:

48 pSS patients with high (n=24) or low (n=24) fatigue were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. After quality control, a total of 383 358 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:

251 differentially methylated CpG sites were associated with fatigue (166 hypomethylated sites annotated to 117 genes and 85 hypermethylated sites annotated to 65 genes). The CpG site with the most pronounced hypomethylation in pSS high fatigue compared with pSS low 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 versus 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 versus low fatigue. These findings point to functional networks that may underlie fatigue. Epigenetic changes could constitute a fatigue-regulating mechanism in chronic inflammatory diseases such as pSS.

Disclosure: K. B. Norheim, None; J. Imgenberg-Kreuz, None; K. Jonsdottir, None; E. Janssen, None; A. C. Syvänen, None; J. K. Sandling, None; G. Nordmark, None; R. Omdal, None.

To cite this abstract in AMA style:

Norheim KB, Imgenberg-Kreuz J, Jonsdottir K, Janssen E, Syvänen AC, Sandling JK, Nordmark G, Omdal R. Epigenome-Wide DNA Methylation Patterns Associated with Fatigue in Primary Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/epigenome-wide-dna-methylation-patterns-associated-with-fatigue-in-primary-sjgrens-syndrome/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/epigenome-wide-dna-methylation-patterns-associated-with-fatigue-in-primary-sjgrens-syndrome/