Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms 英文参考文献.docVIP

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Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms 英文参考文献.doc

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Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms 英文参考文献

ResponsePredictioninChronicHepatitisCby AssessmentofIP-10andIL28B-RelatedSingleNucleotide Polymorphisms MartinLagging1*,GaliaAskarieh1,FrancescoNegro2,StephanieBibert3,JonasSo¨derholm1 ,Johan Westin1,MagnusLindh1,AnaRomero1,GabrieleMissale4,CarloFerrari4,AvidanU.Neumann5 ,Jean- MichelPawlotsky6,BartL.Haagmans7,StefanZeuzem8,Pierre-YvesBochud3.,KristofferHellstrand1. , fortheDITTO-HCVStudyGroup 1DepartmentofInfectiousDiseases/Virology,UniversityofGothenburg,Gothenburg,Sweden,2UniversityHospitalofGeneva,Geneva,Switzerland,3InfectiousDiseases Service, University Hospital and University of Lausanne, Lausanne, Switzerland, 4Azienda Ospedaliera di Parma, Parma, Italy, 5Bar-Ilan University, Ramat-Gan, Israel, 6Ho?pital Henri Mondor - Universite′ Paris XII, Cre′teil, France, 7Department of Virology, Erasmus MC, Rotterdam, The Netherlands, 8Department of Medicine I, J. W. GoetheUniversityHospital,Frankfurt,Germany Abstract Background:HighbaselinelevelsofIP-10predictaslowerfirstphasedeclineinHCVRNAandapooroutcomefollowing interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms(SNPs)adjacenttoIL28BpredictspontaneousresolutionofHCVinfectionandoutcomeoftreatmentamong HCVgenotype1infectedpatients. Methods and Findings: In the present study, we correlated the occurrence of variants at three such SNPs (r randrs8099917)withpretreatmentplasmaIP-10andHCVRNAthroughouttherapywithinaphaseIIItreatment trial(HCV-DITTO)involving253Caucasianpatients.ThefavorableSNPvariants(CC,AA,andTT,respectively)wereassociated withlowerbaselineIP-10(P=0.02,P=0.01,P=0.04)andwerelesscommonamongHCVgenotype1infectedpatientsthan genotype2/3(P,0.0001,P,0.0001,andP=0.01).PatientscarryingfavorableSNPgenotypeshadhigherbaselineviralload thanthose carrying unfavorable variants (P=0.0013, P=0.029, P=0.0004 respectively). Among HCVgenotype 1 infected carriersofthefavorableC,A,orTalleles,IP-10below150pg/mLsignificantlypre