Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease.docVIP
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Genome-scalecase-controlanalysisofCD4T-cellDNAmethylationinjuvenileidiopathicarthritisrevealspotentialtargetsinvolvedindisease
Ellisetal.ClinicalEpigenetics2012,4:20
/content/4/1/20
RESEARCH
OpenAccess
Genome-scalecase-controlanalysisofCD4+T-cell
DNAmethylationinjuvenileidiopathicarthritis
revealspotentialtargetsinvolvedindisease
JustineAEllis1,8*,JaneEMunro2,3,RaulAChavez1,LaviniaGordon4,JihoonEJoo5,6,JonathanDAkikusa2,3,
RogerCAllen2,3,Anne-LouisePonsonby7,JeffreyMCraig5andRichardSaffery6
Abstract
Background:JuvenileIdiopathicArthritis(JIA)isacomplexautoimmunerheumaticdiseaseoflargelyunknown
cause.Evidenceisgrowingthatepigeneticvariation,particularlyDNAmethylation,isassociatedwithautoimmune
disease.However,nothingiscurrentlyknownaboutthepotentialroleofaberrantDNAmethylationinJIA.Asafirst
steptoaddressingthisknowledgegap,wehaveprofiledDNAmethylationinpurifiedCD4+TcellsfromJIA
subjectsandcontrols.GenomicDNAwasisolatedfromperipheralbloodCD4+Tcellsfrom14oligoarticularand
polyarticularJIAcaseswithactivedisease,andhealthyage-andsex-matchedcontrols.Genome-scalemethylation
analysiswascarriedoutusingtheIlluminaInfiniumHumanMethylation27BeadChip.Methylationdataat25,000
CpGswascomparedinacase-controlstudydesign.
Results:Methylationlevelsweresignificantlydifferent(FDRadjustedp0.1)at145loci.Removaloffoursamples
exposedtomethotrexatehadastrikingimpactontheoutcomeoftheanalysis,reducingthenumberof
differentiallymethylatedlocito11.Themethotrexate-naiveanalysisidentifiedreducedmethylationatthegene
encodingthepro-inflammatorycytokineIL32,whichwassubsequentlyreplicatedusingasecondanalysisplatform
andasecondsetofcase-controlpairs.
Conclusions:OurdatasuggeststhatdifferentialTcellDNAmethylationmaybeafeatureofJIA,andthatreduced
methylationatIL32isassociatedwiththisdisease.Furtherworkinlargerprospectiveandlongitudinalsample
collectionsisrequiredtoconfirmthesefindings,assesswhethertheidentifieddifferencesarecausalor
consequentialofdisease,andfurtherinvestigatetheepigeneticmodifyingpropertiesoftherapeuticregimens.
Keywords:Epigenetics,Juvenileidiopathicarthritis,DNAmethylation,Autoimmunity,Methylome,Methotrexate
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