graves病易感基因的筛查和功能初步研究

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1、Next，theexonsandpromotersof1genesinthe1．0Mbregionsurroundingrsl368408wereresequencedand83SNPswererevealed．Inaddition，39SNPsintheintergenicsequencesofsameregion，distributedwithanapproximateintervalof5Kb，wereselectedfromNCBIdbSNP．Thus，atotalof122SNPswithi

2、nthe1．0MbregionwereassayedforallelefrequenciesusingMassarrayinpopulationsofShandongprovinceandthecityofShanghai，China．Bycase—controlanalysis，wefoundtherewere20，24and20SNPsexhibitingsignificantlydifferentallelefrequenciesinthepopulationofShandong，Shangha

3、iandcombinedpopulationrespectively,andthemostsignificantassociationsignalallresidedinthepromoterofUGRP1gene．Then，weusedsothcarePhasetoanalyzethehaplotypesofUGRP1geneintwopopulmionsandcombinedpopulation．Theresultstronglysuggestedthatthehaplotypescomposed

4、ofP1+P2orP1+P3allelesmayconfersusceptibilitytoGD．Atthesametime，twolocuslogisticregressionmodelanalysisinShandongpopulmionconfirmedthatP1andP2SNPsiIlthepromoterofUGRP1genemaybethecausalvariantsofGD．IntwolargernumberofHanpopulationsfromNorthandSouthChinaa

5、ndtwominorityethnicgroupsHasakeandWeiwuerpopulationsfromXinjiangautonomousregion，weverifiedourresults：UGRP1wasalsoasusceptibilitygeneofGDintheseregions．InordertolutherstudytherelationshipbetweenUGRP1geneandpathogenesisofGD，wefirsttestedinvivo．Byconstruc

6、tingthepromoter／luciferasereporterplasmidscontainingdifferentSNPorhaplotypechangesinUGRP1gene’Spromoter,weshowedthattranscriptionactivitiesofUGRP1genepromoterwithPI+P2orPl+P3haplotypeweredecreasedascomparedtonormalsubjects．Meanwhile，byusingelectrophoret

7、icmobilityshiRassays(EMSAs)，weconcludedthatthesusceptibleallelesoftheP1一P3SNPsaffectedbindingoftranscriptionfactors．Furthermore，weverifiedthisfindinginvitro．RealtimePCRandallele·specifictranscriptquantification(ASTQ)experimentsrevealedthattheexpressions

8、ofUGRP1geneinthethyroidtissuesampleswithP1+P2orPI+P3allelesweresignificantlydecreased，ascomparedtothepatientswithwildtypealleles．Ofnote，RT-PCRconfirmedthatMARCO，areceptorforUGRP1gene，Wasexpressedinseveralimmunity—associatedtissue