{"id":11999,"date":"2017-02-28T08:28:41","date_gmt":"2017-02-28T08:28:41","guid":{"rendered":"http:\/\/wames.org.uk\/cms-english\/?p=11999"},"modified":"2017-04-08T09:34:55","modified_gmt":"2017-04-08T09:34:55","slug":"epigenetic-modifications-glucocorticoid-sensitivity-in-mecfs","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/epigenetic-modifications-glucocorticoid-sensitivity-in-mecfs\/","title":{"rendered":"Epigenetic modifications &#038; glucocorticoid sensitivity in ME\/CFS"},"content":{"rendered":"<h3><strong>Research abstract:<\/strong><\/h3>\n<p><strong>Background:<\/strong> Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome<\/p>\n<p>(ME\/CFS) is a debilitating <a href=\"https:\/\/en.wikipedia.org\/wiki\/Idiopathy\" target=\"_blank\">idiopathic<\/a> disease characterized by unexplained fatigue that fails to resolve with sufficient rest.<\/p>\n<p>Diagnosis is based on a list of symptoms and exclusion of other fatigue-related health conditions. Despite a <a href=\"https:\/\/en.wikipedia.org\/wiki\/Homogeneity_and_heterogeneity\" target=\"_blank\">heterogeneous<\/a> 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. <a href=\"http:\/\/www.whatisepigenetics.com\/fundamentals\/\" target=\"_blank\">Epigenetic<\/a> modifications, such as CpG methylation, are known to regulate long-term phenotypic differences and previous work by our group found DNA <a href=\"https:\/\/en.wiktionary.org\/wiki\/methylome\" target=\"_blank\">methylome<\/a> differences in ME\/CFS, however the relationship between DNA methylome modifications, clinical and functional characteristics associated with ME\/CFS has not been examined.<\/p>\n<p><strong>Methods:<\/strong> We examined the DNA methylome in <a href=\"https:\/\/en.wikipedia.org\/wiki\/Peripheral_blood_mononuclear_cell\" target=\"_blank\">peripheral blood mononuclear cells <\/a>(PBMCs) of a larger cohort of female ME\/CFS patients using the <a href=\"https:\/\/www.illumina.com\/products\/methylation_450_beadchip_kits.html\" target=\"_blank\">Illumina HumanMethylation450 BeadChip Array<\/a>. In parallel to the DNA methylome analysis, we investigated in vitro <a href=\"http:\/\/www.nature.com\/nrendo\/journal\/v9\/n11\/full\/nrendo.2013.183.html\" target=\"_blank\">glucocorticoid sensitivity<\/a> differences by stimulating PBMCs with <a href=\"https:\/\/en.wikipedia.org\/wiki\/Phytohaemagglutinin\" target=\"_blank\">phytohaemagglutinin<\/a> and suppressed growth with <a href=\"https:\/\/en.wikipedia.org\/wiki\/Dexamethasone\" target=\"_blank\">dexamethasone.<\/a><\/p>\n<p>We explored DNA methylation differences using <a href=\"http:\/\/bitesizebio.com\/19008\/how-bisulfite-pyrosequencing-works\/\" target=\"_blank\">bisulfite pyrosequencing<\/a> and statistical permutation. <a href=\"https:\/\/en.wikipedia.org\/wiki\/Linear_regression\" target=\"_blank\">Linear regression<\/a> was implemented to discover epigenomic regions associated with self-reported quality of life and network analysis of gene ontology terms to biologically contextualize results.<\/p>\n<p><strong>Results:<\/strong> 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.<\/p>\n<p><strong>Conclusions:<\/strong> Our results indicate DNA methylation modifications in cellular metabolism in ME\/CFS despite a heterogeneous patient population, implicating these processes in immune and <a href=\"https:\/\/en.wikipedia.org\/wiki\/Hypothalamic%E2%80%93pituitary%E2%80%93adrenal_axis\" target=\"_blank\">HPA axis dysfunction<\/a> 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.<\/p>\n<p><a href=\"http:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-017-0248-3\" target=\"_blank\">Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis\/ Chronic Fatigue Syndrome (ME\/CFS)<\/a>\u00a0by Wilfred C. de Vega, Santiago Herrera, Suzanne D. Vernon and Patrick O. McGowan <span style=\"text-decoration: underline;\">in <\/span><em>BMC Medical Genomics<\/em> 2017 10:11 [Published: 23 February 2017]<\/p>\n<p><strong>University of Toronto<\/strong> news, by Don Campbell,\u00a0 4 April 2017:\u00a0<a href=\"https:\/\/www.utoronto.ca\/news\/u-t-study-offers-hope-sufferers-chronic-fatigue-syndrome\" target=\"_blank\">University of Toronto study offers hope to sufferers of chronic<\/a>\u00a0fatigue syndrome<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Research 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 &hellip; <a href=\"https:\/\/wames.org.uk\/cms-english\/epigenetic-modifications-glucocorticoid-sensitivity-in-mecfs\/\">Continue reading <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":true,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[2007,1009,35,1112,587,1033,3535,3536,1111],"class_list":["post-11999","post","type-post","status-publish","format-standard","hentry","category-news","tag-dna-methylation","tag-dr-patrick-o-mcgowan","tag-dr-suzanne-vernon","tag-epigenetics","tag-glucocorticoid-sensitivity","tag-hpa-axis-functioning","tag-innune-cells","tag-santiago-herrera","tag-wilfred-c-de-vega"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-37x","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/11999","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=11999"}],"version-history":[{"count":3,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/11999\/revisions"}],"predecessor-version":[{"id":12554,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/11999\/revisions\/12554"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=11999"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=11999"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=11999"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}