Promoter Hypermethylation of GATA3, IL-4, and TGF-?2 Confers Susceptibility to Vogt-Koyanagi-Harada Disease in Han ChineseHypermethylation of GATA3, IL-4, and TGF-?2 in VKH Disease

摘要

Purpose:Weinvestigatedtheroleofpromotermethylationoftranscriptionalandinflammatoryfactors,includingTBX21,GATA3,ROR?3t,FOXP3,IFN-?3,IL-4,IL-17A,andTGF-?2inthedevelopmentofVogt-Koyanagi-Harada(VKH)disease.Methods:ThepromotermethylationlevelsweredetectedbytheSequenomMassARRAYsysteminCD4+Tcellsthatwereseparatedfrom20healthyindividualsand32VKHpatients(20intheactivestagewithoutmedication,12ininactivestagewithmedication).ThemRNAexpressionlevelofGATA3,IL-4,andTGF-?2inCD4+Tcellswasanalyzedbyreal-timeRT-PCR.Results:ThepromotermethylationlevelsofGATA3,IL-4,andTGF-?2weresignificantlyhigherinactiveVKHpatientsthaninhealthyindividuals(P0.05).AdecreasedmRNAexpressionofGATA3andTGF-?2wasfoundinactiveVKHpatients,whichwascorrelatednegativelywiththeDNAmethylationofthesefactors.TreatmentwithsystemiccorticosteroidandcyclosporinA(CsA)decreasedthemethylationlevelofGATA3andTGF-?2inassociationwithanincreasedmRNAexpressionofmoleculesandreduceddiseaseactivity.Conclusions:OurfindingssuggestthatpromoterhypermethylationofGATA3andTGF-?2inCD4+TcellsconfersrisktoVKHdiseaseinHanChinese.