Functional Polymorphisms in IL13 Are Protective against High Schistosoma mansoni Infection Intensity in a Brazilian Population 英文参考文献.docVIP

FunctionalPolymorphismsinIL13AreProtectiveagainst HighSchistosomamansoniInfectionIntensityin aBrazilianPopulation AudreyV.Grant1,2*,MariaIlmaAraujo3,EduardoVieiraPonte4,RicardoRiccioOliveira3,PeisongGao2, AlvaroA.Cruz3,4,KathleenC.Barnes1,2,TerriH.Beaty1 1DepartmentofEpidemiology,BloombergSchoolofPublicHealth,TheJohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica,2DivisionofAllergyand Clinical Immunology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, United States of America, 3Servic?o de Imunologia, Hospital Universita′rio Professor Edgard Santos, Salvador, Bahia, Brazil, 4Programa para o Controle da Asma e Rinite Ale′rgica na Bahia, Federal University of Bahia School of Medicine,Salvador,Bahia,Brazil Abstract Background: IL-13 is a signature cytokine of the helper T cell type 2 (TH2) pathway which underlies host defense to helminthicinfection andactivates production ofIgE in both parasitized populations and inurban settingsafter allergen exposure. Methodology/Principal Findings: Two functional polymorphisms in IL13, rs1800925 (or c.1-1111C.T) and rs20541 (or R130Q) were previously found to be associated with Schistosoma hematobium infection intensity. They have not been thoroughly explored in S. mansoni-endemic populations, however, and were selected along with 5 tagging SNPs for genotyping in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area of Conde, Bahia, in Brazil. RegressionmodelsusingGEEtoaccountforfamilymembershipandfamily-basedquantitativetransmissiondisequilibrium tests(QTDT)wereusedtoevaluateassociationswithtotalserumIgE(tIgE)levelsandS.mansonifecaleggcountsadjusted fornon-geneticcovariates.WeidentifiedaprotectiveeffectfortheTalleleatrs20541(P=0.005)againsthighS.mansoni eggcounts,corroboratedbyQTDT(P=0.014).OurfindingsalsosuggestedevidenceforprotectiveeffectsfortheTalleleat rs1800925andAalleleatrs2066960afterGEEanalysisonly(P=0.050,0.0002). Conclusions/Significance: The two functional