DNA methylation modifications associated with chronic fatigue syndrome

• Published in: PloS one 2014-08, Vol.9 (8), p.e104757-e104757
• Main Authors: de Vega, Wilfred C, Vernon, Suzanne D, McGowan, Patrick O
• Format: Article
• Language: English
• Subjects: Adult; Biology and life sciences; Chronic fatigue syndrome; CpG Islands - genetics; Deoxyribonucleic acid; Disabilities; DNA; DNA Methylation; DNA probes; Epigenetics; Fatigue; Fatigue Syndrome, Chronic - genetics; Female; Gene expression; Gene Ontology; Gene Regulatory Networks; Gene sequencing; Genes; Genomes; Humans; Immune response; Immune system; Kinases; Leukocytes (mononuclear); Long-term effects; Male; Metabolism; Network analysis; Peripheral blood mononuclear cells; Probes; Regulatory sequences
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104757

Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO) and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology.