Katrine Brække Norheim1, Juliana Imgenberg-Kreuz2, Kristin Jonsdottir3, Emiel A M Janssen3, Ann-Christine Syvänen2, Johanna K Sandling4, Gunnel Nordmark5, Roald Omdal6. 1. Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway katnorheim@gmail.com. 2. Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 3. Department of Pathology, Stavanger University Hospital, Stavanger, Norway. 4. Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 5. Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 6. Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
Abstract
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.
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 pSSpatients 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-fatiguepatients 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 pSSpatients 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.
Authors: Kah Poh Loh; Chandrika Sanapala; Michelle Janelsins; Heidi D Klepin; Rebecca Schnall; Eva Culakova; Michael B Sohn; Paula Vertino; Martha Susiarjo; Marielle Jensen-Battaglia; Michael W Becker; Jane Liesveld; Jason H Mendler; Eric Huselton; Po-Ju Lin; Karen Mustian Journal: J Geriatr Oncol Date: 2021-12-21 Impact factor: 3.929
Authors: Solveig K Hammonds; Maria B Lauvsnes; Ingvild Dalen; Mona K Beyer; Kathinka D Kurz; Ole J Greve; Katrine B Norheim; Roald Omdal Journal: Rheumatol Adv Pract Date: 2017-10-17
Authors: Katrine Brække Norheim; Juliana Imgenberg-Kreuz; Andrei Alexsson; Svein Joar Auglænd Johnsen; Kjetil Bårdsen; Johan Gorgas Brun; Rezvan Kiani Dehkordi; Elke Theander; Thomas Mandl; Roland Jonsson; Wan-Fai Ng; Christopher J Lessard; Astrid Rasmussen; Kathy Sivilis; Lars Ronnblom; Roald Omdal Journal: RMD Open Date: 2021-12