Multiple Sclerosis Susceptibility-Associated SNPs Do Not Influence Disease Severity Measures in a Cohort of Australian MS Patients 英文参考文献.docVIP

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Multiple Sclerosis Susceptibility-Associated SNPs Do Not Influence Disease Severity Measures in a Cohort of Australian MS Patients 英文参考文献.doc

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Multiple Sclerosis Susceptibility-Associated SNPs Do Not Influence Disease Severity Measures in a Cohort of Australian MS Patients 英文参考文献

MultipleSclerosisSusceptibility-AssociatedSNPsDoNot InfluenceDiseaseSeverityMeasuresinaCohortof AustralianMSPatients CathyJ.Jensen1,2,JimStankovich3,AnnekeVanderWalt4,5,6,MelanieBahlo7,BruceV.Taylor3, IngridA.F.vanderMei3,SimonJ.Foote3,TrevorJ.Kilpatrick5,LauraJ.Johnson1,EllaWilkins1 ,Judith Field1,PatrickDanoy8,MatthewABrown8,9,fortheTheAustralianandNewZealandMultipleSclerosis GeneticsConsortium(ANZgene)¤,JustinP.Rubio1,HelmutButzkueven1,4,6* 1HowardFloreyInstitute,Melbourne,Australia,2PhysiologyDepartment,FacultyofMedicine,NursingandHealthSciences,MonashUniversity,Melbourne,Australia, 3MenziesResearchInstitute,UniversityofTasmania,Hobart,Australia,4TheRoyalMelbourneHospital,Melbourne,Australia,5CentreforNeuroscience,Universityof Melbourne, Melbourne, Australia, 6The Box Hill Hospital, Box Hill, Victoria, Australia, 7The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, 8DiamantinaInstituteofCancer,ImmunologyandMetabolicMedicine,PrincessAlexandraHospital,UniversityofQueensland,Brisbane,Queensland,Australia,9Botnar ResearchCentre,NuffieldDepartmentofOrthopaedicSurgery,UniversityofOxford,Oxford,UnitedKingdom Abstract Recentassociationstudiesinmultiplesclerosis(MS)haveidentifiedandreplicatedseveralsinglenucleotidepolymorphism (SNP)susceptibilitylociincludingCLEC16A,IL2RA,IL7R,RPL5,CD58,CD40andchromosome12q13–14inadditiontothewell established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity,asdemonstratedpreviouslyfortheMSriskalleleHLA-DR15.Weinvestigatedthishypothesisinacohortof1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towardsassociationbetweentheRPL5riskSNPandtimebetweenfirstdemyelinatingeventandrelapse,andbetweenthe CD40riskSNPandsymboldigittestscore.Noassociationsweresignifica