Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA) 英文参考文献.docVIP

AssociationoftheIL-10GeneFamilyLocuson Chromosome1withJuvenileIdiopathicArthritis(JIA) EbunOmoyinmi1*.,PaolaForabosco2.,RajaHamaoui1,AnnetteBryant1,AnneHinks3,SimonaUrsu4, ChildhoodArthritisProspectiveStudy(CAPS){,BSPARstudygroup{,ChildhoodArthritisResponseto MedicationStudy(CHARMS){,LucyR.Wedderburn4,WendyThomson3,CathrynM.Lewis5,6, PatriciaWoo1 1DepartmentofImmunologyandMolecularPathology,UniversityCollegeLondon,London,UnitedKingdom,2IstututodiGeneticadellePopolazioni,CNR,Sassari,Italy, 3ArthritisResearchUKEpidemiologyUnit,ManchesterAcademicHealthScienceCentre,TheUniversityofManchester,Manchester,UnitedKingdom,4Rheumatology Unit,InstituteofChildHealth,UniversityCollegeLondon,London,UnitedKingdom,5King’sCollegeLondon,DepartmentofMedicalandMolecularGenetics,London, UnitedKingdom,6King’sCollegeLondon,MRCSGDPCentre,InstituteofPsychiatry,London,UnitedKingdom Abstract Background: The cytokine IL-10 and its family members have been implicated in autoimmune diseases and we have previouslyreportedthatgeneticvariantsinIL-10wereassociatedwithararegroupofdiseasescalledjuvenileidiopathic arthritis(JIA).TheaimofthisstudywastofinemapgeneticvariantswithintheIL-10cytokinefamilyclusteronchromosome 1 using linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (tSNPs) approach with imputation and conditionalanalysistotestfordiseaseassociations. Methodology/PrincipalFindings:Fifty-threetSNPsweretestedforassociationbetweenCaucasianpaediatriccohorts[219 systemic JIA (sJIA), 187 persistent oligoarticular JIA (pOJIA), and 139 extended OJIA (eOJIA) patients], and controls (WellcomeTrustcontrolcohort,WTCCC2).SignificantassociationwithsJIAwasdetectedatrs1400986inthepromoterofIL- 20 (odds ratio 1.53; 95% CI 1.21–1.93; p=0.0004), but in no other subtypes. Imputation analysis identified additional associated SNPs for pOJIA at IL-20 and IL-24, including a rare, functional, missense variant at IL-24 with a p=0.0002. PenalisedlogisticregressionanalysiswithHyperLassoandconditionalan