Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author ANDRADE, Daniel Ciampi de FMUSP-HC
MASCHIETTO, Mariana
GALHARDONI, Ricardo FMUSP-HC
GOUVEIA, Gisele FMUSP-HC
CHILE, Thais FMUSP-HC
KREPISCHI, Ana C. Victorino
DALE, Camila S. FMUSP-HC
BRUNONI, Andre R. FMUSP-HC
PARRAVANO, Daniella C. FMUSP-HC
MOSCOSO, Ana S. Cueva FMUSP-HC
RAICHER, Irina FMUSP-HC
KAZIYAMA, Helena H. S. FMUSP-HC
TEIXEIRA, Manoel J. FMUSP-HC
BRENTANI, Helena P. FMUSP-HC
dc.date.issued 2017
dc.identifier.citation PAIN, v.158, n.8, p.1473-1480, 2017
dc.identifier.issn 0304-3959
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/21927
dc.description.abstract To evaluate changes in DNA methylation profiles in patients with fibromyalgia (FM) compared to matched healthy controls (HCs). All individuals underwent full clinical and neurophysiological assessment by cortical excitability (CE) parameters measured by transcranial magnetic stimulation. DNA from the peripheral blood of patients with FM (n = 24) and HC (n = 24) were assessed using the IlluminaHumanMethylation450 BeadChips. We identified 1610 differentially methylated positions (DMPs) in patients with FM displaying a nonrandom distribution in regions of the genome. Sixty-nine percent of DMP in FM were hypomethylated compared to HC. Differentially methylated positions were enriched in 5 genomic regions (1p34; 6p21; 10q26; 17q25; 19q13). The functional characterization of 960 genes related to DMPs revealed an enrichment for MAPK signaling pathway (n 5 18 genes), regulation of actin cytoskeleton (n = 15 genes), and focal adhesion (n = 13 genes). A gene-gene interaction network enrichment analysis revealed the participation of DNA repair pathways, mitochondria-related processes, and synaptic signaling. Even though DNA was extracted from peripheral blood, this set of geneswas enriched for disorders such as schizophrenia, mood disorders, bulimia, hyperphagia, and obesity. Remarkably, the hierarchical clusterization based on the methylation levels of the 1610 DMPs showed an association with neurophysiological measurements of CE in FM and HC. Fibromyalgia has a hypomethylation DNA pattern, which is enriched in genes implicated in stress response and DNA repair/free radical clearance. These changes occurred parallel to changes in CE parameters. New epigenetic insights into the pathophysiology of FM may provide the basis for the development of biomarkers of this disorder.
dc.description.sponsorship · Pain Center, Neurology Department, University of Sao Paulo
· Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
dc.language.iso eng
dc.publisher LIPPINCOTT WILLIAMS & WILKINS
dc.relation.ispartof Pain
dc.rights restrictedAccess
dc.subject Fibromyalgia; Chronic pain; Cortical excitability; DNA methylation; Epigenetics
dc.subject.other symptom severity; clinical pain; injury model; methylation; survival; excitability; depression; cytokines
dc.title Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study
dc.type article
dc.rights.holder Copyright LIPPINCOTT WILLIAMS & WILKINS
dc.description.group LIM/26
dc.description.group LIM/21
dc.description.group LIM/23
dc.description.group LIM/27
dc.identifier.doi 10.1097/j.pain.0000000000000932
dc.identifier.pmid 28621701
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author ANDRADE, Daniel Ciampi de:HC:ICHC
hcfmusp.author GALHARDONI, Ricardo:FM:
hcfmusp.author GOUVEIA, Gisele:FM:MPS
hcfmusp.author CHILE, Thais:HC:IPQ
hcfmusp.author DALE, Camila S.:HC:LIM/26
hcfmusp.author BRUNONI, Andre R.:HC:IPQ
hcfmusp.author PARRAVANO, Daniella C.:HC:IPQ
hcfmusp.author MOSCOSO, Ana S. Cueva:HC:IMREA
hcfmusp.author RAICHER, Irina:HC:ICESP
hcfmusp.author KAZIYAMA, Helena H. S.:HC:IOT
hcfmusp.author TEIXEIRA, Manoel J.:FM:MNE
hcfmusp.author BRENTANI, Helena P.:FM:MPS
hcfmusp.author.external · MASCHIETTO, Mariana:Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP, Brazil
· KREPISCHI, Ana C. Victorino:Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Sao Paulo, Brazil
hcfmusp.origem.id WOS:000406932300011
hcfmusp.origem.id 2-s2.0-85026303090
hcfmusp.publisher.city PHILADELPHIA
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
dc.identifier.eissn 1872-6623
hcfmusp.citation.scopus 11
hcfmusp.citation.wos 12
hcfmusp.affiliation.country Brasil


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