Genetic Variation of the Fc Gamma Receptor 3B Gene and Association with Rheumatoid Arthritis 英文参考文献.docVIP

GeneticVariationoftheFcGammaReceptor3BGene andAssociationwithRheumatoidArthritis RuteB.Marques1*.,MohamedM.Thabet1,2.,StefanJ.White3,JeanineJ.Houwing-Duistermaat4, AleidaM.Bakker1,Gert-JanHendriks1,AlexandraZhernakova1,TomW.Huizinga1,AnnetteH.vander Helm-vanMil1,ReneE.Toes1 1DepartmentofRheumatology,LeidenUniversityMedicalCenter,Leiden,TheNetherlands,2DepartmentofInternalMedicine,AssiutUniversityHospital,Assiut,Egypt, 3MolecularDevelopment,MurdochChildrensResearchInstitute,Melbourne,Australia,4DepartmentofMedicalStatistics,LeidenUniversityMedicalCenter,Leiden,The Netherlands Abstract Background:Fcgammareceptors(FccRs)playacrucialroleinimmunitybylinkingIgGantibody-mediatedresponseswith cellulareffectorandregulatoryfunctions.Geneticvariantsinthesereceptorshavebeenpreviouslyidentifiedasriskfactors forseveralchronicinflammatoryconditions.Thepresentstudyaimedtoinvestigatethepresenceofcopynumbervariations (CNVs)intheFCGR3Bgeneanditspotentialassociationwiththeautoimmunediseaserheumatoidarthritis(RA). Methodology/Principal Findings: CNV of the FCGR3B gene was studied using Multiplex Ligation Dependent Probe Amplification (MLPA) in 518 Dutch RA patients and 304 healthy controls. Surprisingly, three independent MLPA probes targetingtheFCGR3BpromotermeasureddifferentCNVfrequencies,withprobe#1and#2measuring0to5genecopies and probe#3 showing little evidence of CNV. Quantitative-PCR correlated with the copy number results from MLPA probe#2,which detectedlow copy number(1copy)in 6.7%andhigh copy number($3 copies) in9.4% ofthecontrol population.NosignificantdifferencewasobservedbetweenRApatientsandthehealthycontrols,neitherinthelowcopy nor the high copy number groups (p-values=0.36 and 0.71, respectively). Sequencing of the FCGR3B promoter region revealedaninsertion/deletion(indel)thatexplainedthedisparateCNVresultsofMLPAprobe#1.Finally,anon-significant trend was found between the novel -256A.TG indel and RA (40.7% in healthy controls versus 35.9% in RA patients; P=0.08). Concl