Differential Combination of Cytokine and Interferon- γ +874 TA Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis 英文参考文献.docVIP

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Differential Combination of Cytokine and Interferon- γ +874 TA Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis 英文参考文献.doc

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DifferentialCombinationofCytokineandInterferon-γ874TAPolymorphismsDeterminesDiseaseSeverityinPulmonaryTuberculosis英文参考文献

DifferentialCombinationofCytokineandInterferon-c +874T/APolymorphismsDeterminesDiseaseSeverityin PulmonaryTuberculosis AmbreenAnsari1,ZahraHasan1,GhaffarDawood2,RabiaHussain1* 1DepartmentofPathologyandMicrobiology,AgaKhanUniversity,Karachi,Pakistan,2MasoomeenTrustHospital,Karachi,Pakistan Abstract Background:Mycobacteriumtuberculosisinfectsnearly1/3oftheworldpopulationandthisreservoirformsthelargestpool from which new cases arise. Among the cytokines, IFN-c is a key determinant in protection against tuberculosis. Single nucleotidepolymorphisms(SNPs)inIFN-cgene(+874T/A)whichdetermineTThigh(hi),AAlow(lo)andTAintermediate(int) responderphenotypeshaveshownvariableassociationswithtuberculosisdiseaseoutcomeindifferentethnicpopulations. TheobjectiveofthecurrentstudywastoanalyzeIFN-cgenecombinationswithotherIFN-cregulatingcytokinegenes(IL- 10,TNF–a,IL-6)toseetheeffectofgene-combinationsondiseaseseverityoutcomeinpulmonarytuberculosis. MethodsandFindings:StudygroupscomprisedofpulmonaryTBpatientsstratifiedaccordingtolungtissueinvolvement into mild (Pmd=74) or advance (Pad=23) lung disease and compared with healthy controls (TBNA=166). Genotype analysiswascarriedoutusingamplificationrefractorymutationsystem-PCR(ARMS-PCR).IFN-cgene(+874T/A)functional SNPcombinationsinTNFa(2308G/A),IL-10(21082A/G)andIL-6(2174G/C)wereanalyzed.Singlegeneanalysis(Pearson x2)showedadominantassociationofIFN-cTT higenotype(p=0.001)andTallele(p=0.001)withmilddisease.IFN-clo-IL- 10lo genotypecombinationwasassociatedwithadvanceddisease(p=0.002).IFN-chi –IL-6 hi combinationwasassociated withmilddisease(p=0.0005)whileIFN-clo–IL-6intwasassociatedwithprotectionagainstbothformsofpulmonarydisease (p=0.002). Conclusion: Our results show that a limited number of IFN-c gene combinations with other cytokine functional SNPs determinetheoutcomeofdiseaseseverityintuberculosis. Citation:AnsariA,HasanZ,DawoodG,HussainR(2011)DifferentialCombinationofCytokineandInterferon-c+874T/APolymorphismsDeterminesDisease S