TLR7 single-nucleotide polymorphisms in the 3 untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women a case-control association study 英文参考文献.docVIP

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TLR7 single-nucleotide polymorphisms in the 3 untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women a case-control association study 英文参考文献.doc

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TLR7 single-nucleotide polymorphisms in the 3 untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women a case-control association study 英文参考文献

Kawasakietal.ArthritisResearchTherapy2011,13:R41 /content/13/2/R41 RESEARCH ARTICLE OpenAccess TLR7single-nucleotidepolymorphismsinthe3’ untranslatedregionandintron2independently contributetosystemiclupuserythematosusin Japanesewomen:acase-controlassociationstudy AyaKawasaki1,HiroshiFurukawa2,YuyaKondo3,SatoshiIto3,4,TaichiHayashi3,MakioKusaoi5,IsaoMatsumoto3, ShigetoTohma2,YoshinariTakasaki5,HiroshiHashimoto6,TakayukiSumida3andNaoyukiTsuchiya1* Abstract Introduction:TheToll-likereceptor7(TLR7)gene,encodedonhumanchromosomeXp22.3,iscrucialfortypeI interferonproduction.ArecentmulticenterstudyinEastAsianpopulations,comprisingChinese,KoreanandJapanese participants,identifiedanassociationofaTLR7single-nucleotidepolymorphism(SNP)locatedinthe3’untranslated region(3’UTR),rs3853839,withsystemiclupuserythematosus(SLE),especiallyinmales,althoughsomedifferencewas observedamongthetestedpopulations.TotestwhetheradditionalpolymorphismscontributetoSLEinJapanese,we systematicallyanalyzedtheassociationofTLR7withSLEinaJapanesefemalepopulation. Methods:Acase-controlassociationstudywasconductedoneighttagSNPsintheTLR7region,including rs3853839,in344JapanesefemaleswithSLEand274healthyfemalecontrols. Results:Inadditiontors3853839,twoSNPsinintron2,rs179019andrs179010,whichwereinmoderatelinkage disequilibriumwitheachother(r2=0.53),showedanassociationwithSLE(rs179019:P=0.016,oddsratio(OR)2.02, 95%confidenceinterval(95%CI)1.15to3.54;rs179010:P=0.018,OR1.75,95%CI1.10to2.80(bothunderthe recessivemodel)).ConditionallogisticregressionanalysisrevealedthattheassociationoftheintronicSNPsandthe3’ UTRSNPremainedsignificantafterweadjustedthemforeachother.Whenonlythepatientsandcontrolscarryingthe riskgenotypesatthe3’UTRSNPpositionwereanalyzed,theriskofSLEwassignificantlyincreasedwhentheindividuals alsocarriedtheriskgenotypesatbothoftheintronicSNPs(P=0.0043,OR2.45,95%CI1.31to4.60).Furthermore,the haplotypecontainingtheintronicriskallelesinadditiontothe3’UTRriskallelewasassociatedwithSLEunderthe recessi