Overlapping genetic susceptibility variants between three autoimmune disorders rheumatoid arthritis, type 1 diabetes and coeliac disease 英文参考文献.docVIP

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Overlapping genetic susceptibility variants between three autoimmune disorders rheumatoid arthritis, type 1 diabetes and coeliac disease 英文参考文献.doc

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Eyreetal.ArthritisResearchTherapy2010,12:R175 /content/12/5/R175 RESEARCH ARTICLE OpenAccess Overlappinggeneticsusceptibilityvariants betweenthreeautoimmunedisorders: rheumatoidarthritis,type1diabetesand coeliacdisease StephenEyre1*,AnneHinks1,JohnBowes1,EdwardFlynn1,PaulMartin1,AnthonyGWilson2,AnnWMorgan3, PaulEmery3,SophiaSteer4,LynneJHocking5,DavidMReid5,PilleHarrison6,PaulWordsworth6, YorkshireEarlyArthritis(YEAR)Consortium,BiologicsinRAControl(BIRAC)Consortium,WendyThomson1, JaneWorthington1,AnneBarton1 Abstract Introduction:Genomewideassociationstudies,replicatedbynumerouswellpoweredvalidationstudies,have revealedalargenumberoflocilikelytoplayaroleinsusceptibilitytomanymultifactorialdiseases.Itisnowwell establishedthatsomeoftheselociaresharedbetweendiseaseswithsimilaraetiology.Forexample,anumberof autoimmunediseaseshavebeenassociatedwithvariantsinthePTPN22,TNFAIP3andCTLA4genes.Herewehave attemptedtodefineoverlappinggeneticvariantsbetweenrheumatoidarthritis(RA),type1diabetes(T1D)and coeliacdisease(CeD). Methods:WeselectedeightSNPspreviouslyidentifiedasbeingassociatedwithCeDandsixT1D-associatedSNPs forvalidationinasampleof3,962RApatientsand3,531controls.GenotypingwasperformedusingtheSequenom MassArrayplatformandcomparisonofgenotypeandallelefrequenciesbetweencasesandcontrolswas undertaken.AtrendtestP-value0.004wasregardedassignificant. Results:WefoundstatisticallysignificantevidenceforassociationoftheTAGAPlocuswithRA(P=5.0×10-4 ).A markeratoneotherlocus,C1QTNF6,previouslyassociatedwithT1D,showednominalassociationwithRAinthe currentstudybutdidnotremainstatisticallysignificantatthecorrectedthreshold. Conclusions:InexploringtheoverlapbetweenT1D,CeDandRA,thereisstrongevidencethatvariationwithin theTAGAPgeneisassociatedwithallthreeautoimmunediseases.Interestinglyanumberoflociappeartobe specifictooneofthethreediseasescurrentlystudiedsuggestingthattheymayplayaroleindeterminingthe particularautoimmunephenotypeatpresentation. Introduction auto-immune, inflammatory dis