Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women 英文参考文献.docVIP

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Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women 英文参考文献.doc

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Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women 英文参考文献

GeneticVariationoftheHumanUrinaryTractInnate ImmuneResponseandAsymptomaticBacteriuriain Women ThomasR.Hawn1*,DeliaScholes2,HongweiWang3,SueS.Li3,AnnE.Stapleton1,MartaJaner4 ,Alan Aderem4,WalterE.Stamm1,LuePingZhao3,ThomasM.Hooton5 1DepartmentofMedicine,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica,2GroupHealthCenterforHealthStudies,GroupHealthCooperative, and Department of Epidemiology, University of Washington, Seattle, Washington, United States of America, 3Fred Hutchinson Cancer Research Center, Seattle, Washington,United StatesofAmerica, 4Institute forSystems Biology,Seattle,Washington, UnitedStates ofAmerica, 5Department ofMedicine,UniversityofMiami, Miami,Florida,UnitedStatesofAmerica Abstract Background:AlthoughseveralstudiessuggestthatgeneticfactorsareassociatedwithhumanUTIsusceptibility,theroleof DNAvariationinregulatingearlyinvivourineinflammatoryresponseshasnotbeenfullyexamined.Weexaminedwhether candidategenepolymorphismswereassociatedwithalteredurineinflammatoryprofilesinasymptomaticwomenwithor withoutbacteriuria. Methodology:Weconductedacross-sectionalanalysisofasymptomaticbacteriuria(ASB)in1,261asymptomaticwomen ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and withoutASB.Wecollectedurinesamplesandmeasuredlevelsofuropathogenicbacteria,neutrophils,andchemokines. PrincipalFindings:PolymorphismTLR2_G2258A,avariantassociatedwithdecreasedlipopeptide-inducedsignaling,was associatedwithincreasedASBrisk(oddsratio3.44,95%CI;1.65–7.17).ThreeCXCR1polymorphismswereassociatedwith ASBcausedbygram-positiveorganisms.ASBwasassociatedwithurinaryCXCL-8levels,butnotCXCL-5,CXCL-6,orsICAM-1 (P#0.0001).UrinarylevelsofCXCL-8andCXCL-6,butnotICAM-1,wereassociatedwithhigherneutrophillevels(P#0.0001). Inaddition,polymorphismCXCR1_G827CwasassociatedwithincreasedCXCL-8levelsinwomenwithA