Association of the Gene Polymorphisms IFN-γ +874, IL-13 ？1055 and IL-4 ？590 with Patterns of Reinfection with Schistosoma mansoni 英文参考文献.docVIP

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Association of the Gene Polymorphisms IFN-γ +874, IL-13 ？1055 and IL-4 ？590 with Patterns of Reinfection with Schistosoma mansoni 英文参考文献.doc

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AssociationoftheGenePolymorphismsIFN-γ874,IL-13？1055andIL-4？590withPatternsofReinfectionwithSchistosomamansoni英文参考文献

AssociationoftheGenePolymorphismsIFN-c+874,IL-13 21055andIL-42590withPatternsofReinfectionwith Schistosomamansoni MichaelR.Gatlin1,CarlaL.Black1,PaulineN.Mwinzi2,W.EvanSecor3,DianaM.Karanja2,DanielG. Colley1* 1University of Georgia, Athens, Georgia, United States of America, 2Kenya Medical Research Institute, Kisumu, Kenya, 3Centers for Disease Control and Prevention, Atlanta,Georgia,UnitedStatesofAmerica Abstract Background:Theimmunologicfindingsthatmostconsistentlycorrelatewithresistanceinhumanschistosomiasisarehigh levelsofIgEandlowlevelsofIgG4.Wehavegenotypedgeneandpromoterpolymorphismsofcytokinesassociatedwith regulation of these isotypes in a cohort of men occupationally exposed to Schistosoma mansoni in western Kenya and evaluated their patterns with respect to resistance and susceptibility to reinfection after treatment and cure with praziquantel(PZQ). Methodology/PrincipalFindings:Inthiscohort,polymorphismsinIL-4(2590ThighIgE),IL-13(21055Thighproducer)and IFN-c(+874Ahighproducer)demonstratedseveralcorrelationswithresistancetoreinfection.Resistancetoreinfectionwas significantlycorrelatedwiththeheterozygousIL-42590genotypeC/T(OR3.5,[CI1.2,10.2])comparedtoT/T.Amongmen with ahomozygous IL-13 genotype CC/TT, having a T allele at the IFN-c +874 position increased theodds of resistance relativetoindividualswiththeIFN-c+874A/Agenotype(OR=17.5[CI3.0,101.5]).AmongmenwithhomozygousA/AIFN-c genotype, the heterozygous IL-13 genotype C/T was associated with resistance relative to the homozygous C/C or T/T genotypes(OR=22.5[CI3.5,144.4]).NoincreasesinoddsofresistancewerefoundinrelationtotheIL-13genotypeamong those with a T allele in the IFN-c gene or in relation to the IFN-c genotype among those with a heterozygous IL-13 genotype.CalculationoftheattributableproportionofresistanceshowedasignificantsynergisticinteractionbetweenIL-13 21055C/TandIL-42590C/T. Conclusions:Theidentifiedpolymorphismsdonotbythemselvesconferresistanceorsusceptibility,butweproposethat thesegenotyp