An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans 英文参考文献.docVIP

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An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans 英文参考文献.doc

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An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans 英文参考文献

AnAfricanAncestry-SpecificAlleleofCTLA4Confers ProtectionagainstRheumatoidArthritisinAfrican Americans JamesM.Kelley1,LauraB.Hughes1,JeffreyD.Faggard1,MariaI.Danila1,MonicaH.Crawford1, YuanqingEdberg1,MiguelA.Padilla1,HemantK.Tiwari1,AndrewO.Westfall1,GracielaS.Alarco′n1, DoytL.Conn2,BethL.Jonas3,LeighF.Callahan3,EdwinA.Smith4,RichardD.Brasington,Jr.5,DavidB. Allison1,RobertP.Kimberly1,LarryW.Moreland1¤,JeffreyC.Edberg1,S.LouisBridges,Jr.1* 1UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica,2EmoryUniversity,Atlanta,Georgia,UnitedStatesofAmerica,3Universityof North Carolina, Chapel Hill, North Carolina, United States of America, 4Medical University of South Carolina, Charleston, South Carolina, United States of America, 5WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica Abstract CytotoxicT-lymphocyteassociatedprotein4(CTLA4)isanegativeregulatorofT-cellproliferation.PolymorphismsinCTLA4 havebeeninconsistentlyassociatedwithsusceptibilitytorheumatoidarthritis(RA)inpopulationsofEuropeanancestrybut havenotbeenexaminedinAfricanAmericans.TheprevalenceofRAinmostpopulationsofEuropeanandAsianancestryis ,1.0%;RAispurportedlylesscommoninblackAfricans,withlittleknownaboutitsprevalenceinAfricanAmericans.We soughttodetermineifCTLA4polymorphismsareassociatedwithRAinAfricanAmericans.Weperformeda2-stageanalysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patientsand712AfricanAmericancontrolsusingIlluminaandTaqManplatforms.Theminorallele(G)ofthers231778SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462610 , Fisher’s exact). The presence of the G allele was associatedwithasubstantiallyreducedoddsratio(OR)ofhavingRA(AG+GGgenotypesvs.AAgenotype,OR0.19,95%CI: 0.13–0.26,p=2.4610 ,Fisher’sexact),suggestingaprotectiveeffect.ThisSNPispolymorphicintheAfricanpopulation (minorallelefrequency[MAF]0.09intheYorubapopulation),butisveryrareinothergroups(MAF=0.002