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23.02.17 - Epigenetische veranderingen en glucocorticoïden gevoeligheid bij ME/CVS

Epigenetische veranderingen en glucocorticoïden gevoeligheid bij ME/CVS


Wilfred C. de Vega, Santiago Herrera, Suzanne D. Vernon and Patrick O. McGowan deden een studie naar mogelijke epigenetische wijzigingen en glucocorticoïden gevoeligheid bij 49 ME/CVS-patiënten en 25 gezonde proefpersonen. De ME/CVS-patiënten voldeden aan de Fukuda-criteria alsook aan de Canadese Consensus criteria.  

Het resultaat van hun onderzoek toonde dat de methylering in ME/CVS in 12.608 plaatsen afweek. In de meeste gevallen zag men hypermethylering die resulteerde in een verminderde genexpressie. 

McGowan en collega's stelden vast dat er bij 14  van de  ME/CVS-patiënten een gevoeligheid voor glucocorticoïden opgemerkt werd maar er eveneens 19 patiënten geen overgevoeligheid vertoonden en er voor deze dus geen verschil was met gezonde proefpersonen. 
De verhoogde gevoeligheid van het afweersysteem voor glucocorticoïden bij de 14 patiënten had een statistisch relatie met afwijkende methylering op 13 verschillende loci in het DNA.


Hieronder de samenvatting (Engels) van deze studie:

Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Wilfred C. de Vega, Santiago Herrera, Suzanne D. Vernon and Patrick O. McGowanEmail author
BMC Medical GenomicsBMC series – open, inclusive and trusted201710:11
DOI: 10.1186/s12920-017-0248-3©  The Author(s). 2017
Published: 23 February 2017
Abstract

Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating idiopathic disease characterized by unexplained fatigue that fails to resolve with sufficient rest. Diagnosis is based on a list of symptoms and exclusion of other fatigue-related health conditions. Despite a heterogeneous patient population, immune and hypothalamic-pituitary-adrenal (HPA) axis function differences, such as enhanced negative feedback to glucocorticoids, are recurring findings in ME/CFS studies. Epigenetic modifications, such as CpG methylation, are known to regulate long-term phenotypic differences and previous work by our group found DNA methylome differences in ME/CFS, however the relationship between DNA methylome modifications, clinical and functional characteristics associated with ME/CFS has not been examined.

Methods
We examined the DNA methylome in peripheral blood mononuclear cells (PBMCs) of a larger cohort of female ME/CFS patients using the Illumina HumanMethylation450 BeadChip Array. In parallel to the DNA methylome analysis, we investigated in vitro glucocorticoid sensitivity differences by stimulating PBMCs with phytohaemagglutinin and suppressed growth with dexamethasone. We explored DNA methylation differences using bisulfite pyrosequencing and statistical permutation. Linear regression was implemented to discover epigenomic regions associated with self-reported quality of life and network analysis of gene ontology terms to biologically contextualize results.

Results
We detected 12,608 differentially methylated sites between ME/CFS patients and healthy controls predominantly localized to cellular metabolism genes, some of which were also related to self-reported quality of life health scores. Among ME/CFS patients, glucocorticoid sensitivity was associated with differential methylation at 13 loci.

Conclusions
Our results indicate DNA methylation modifications in cellular metabolism in ME/CFS despite a heterogeneous patient population, implicating these processes in immune and HPA axis dysfunction in ME/CFS. Modifications to epigenetic loci associated with differences in glucocorticoid sensitivity may be important as biomarkers for future clinical testing. Overall, these findings align with recent ME/CFS work that point towards impairment in cellular energy production in this patient population.










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