Polymorphic Variation in TIRAP Is Not Associated with Susceptibility to Childhood TB but May Determine Susceptibility to TBM in Some Ethnic Groups 英文参考文献.docVIP
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Polymorphic Variation in TIRAP Is Not Associated with Susceptibility to Childhood TB but May Determine Susceptibility to TBM in Some Ethnic Groups 英文参考文献
PolymorphicVariationinTIRAPIsNotAssociatedwith
SusceptibilitytoChildhoodTBbutMayDetermine
SusceptibilitytoTBMinSomeEthnicGroups
ShobanaRebeccaDissanayeke1,SamuelLevin1,SandraPienaar2,KathrynWood3,BrianEley2 ,David
Beatty2,HowardHenderson2,SuzanneAnderson1,MichaelLevin1*
1DepartmentofPaediatricInfectiousDiseases,ImperialCollegeLondon,London,UnitedKingdom,2PaediatricInfectiousDiseasesUnit,RedCrossChildren’sHospital,
SchoolofChildandAdolescentHealth,UniversityofCapeTown,CapeTown,SouthAfrica,3InstituteofInfectiousDiseasesandMolecularMedicine,FacultyofHealth
Sciences,UniversityofCapeTown,CapeTown,SouthAfrica
Abstract
Hostrecognitionofmycobacterialsurfacemoleculesoccursthroughtolllikereceptors(TLR)2and6.Theadaptorprotein
TIRAPmediatesdownstreamsignallingofTLR2and4,andpolymorphismsintheTIRAPgene(TIRAP)havebeenassociated
withsusceptibilityandresistancetotuberculosis(TB)inadults.Inordertoinvestigatetheroleofpolymorphicvariationin
TIRAPinchildhoodTBinSouthAfrica,whichhasoneofthehighestTBincidenceratesintheworld,wescreenedtheentire
openreadingframeofTIRAPforsequencevariationintwocohortsofchildhoodTBfromdifferentethnicgroups(Xhosaand
mixedancestry).Weidentified13SNPs,includingsevenpreviouslyunreported,inthetwocohorts,andfoundsignificant
differencesinfrequencyofthevariantsbetweenthetwoethnicgroups.Nodifferencesinfrequencybetweenindividual
SNPsorcombinationswerefoundbetweenTBcasesandcontrolsineithercohort.Howeverthe558CRTSNPpreviously
associatedwithTBmeningitis(TBM)inaVietnamesepopulationwasfoundtobeassociatedwithTBMinthemixedancestry
group.PolymorphismsinTIRAPdonotappeartobeinvolvedinchildhoodTBsusceptibilityinSouthAfrica,butmayplaya
roleindeterminingoccurrenceofTBM.
Citation:DissanayekeSR,LevinS,PienaarS,WoodK,EleyB,etal.(2009)PolymorphicVariationinTIRAPIsNotAssociatedwithSusceptibilitytoChildhoodTBbut
MayDetermineSusceptibilitytoTBMinSomeEthnicGroups.PLoSONE4(8):e6698.doi:10.1371/journal.pone.0006698
Editor:BenMarais,UniversityofStellenbosch,SouthAfrica
ReceivedMay28,2009;Ac
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