gata2 tagsnps与中国汉族冠心病群体易感性分析-gata 2 tags nps and susceptibility analysis of coronary heart disease in chinese han population.docx

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2018-06-04 发布于上海
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gata2 tagsnps与中国汉族冠心病群体易感性分析-gata 2 tags nps and susceptibility analysis of coronary heart disease in chinese han population.docx

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gata2 tagsnps与中国汉族冠心病群体易感性分析-gata 2 tags nps and susceptibility analysis of coronary heart disease in chinese han population

AbstractCoronaryarterydisease(CAD)iscausedbyaccumulationoflipidsandother inflammatorymoleculesinthecoronaryarteries,whichmayeventuallyleadtoformation ofplaques(atherosclerosis)andblockageorstenosisofbloodflow,resultinischemiaand myocardialinfarction(MI).CADisacomplexdiseasewhichcausessignificantmorbidity andmortalityworldwide.InChinaCADcausesmorethan80milliondeathseachyearin. Itisamulti-genecomplexgeneticdiseasecausedbygeneticandenvironmentalfactors, and theirinteractions.ThefirstGWASintheChinesepopulationidentifiedoneSNPinaputativegene c6orf105(rs6903956)thatwassignificantlyassociatedwithriskofCADandMI. Real-timereversetranscriptionPCRanalysis(RT-PCR)foundthattheexpressionlevelof c6orf105mRNAwassignificantlydecreasedintheAGorAAgenotype.Further studiesin ourLaboratoryfoundthattheexpressionlevelofc6orf105wasregulated by transcriptionalfactorGATA2atthetranscriptionallevel.Basedonthesedata,I hypothesizedthatSNPsinGATA2weassociatedwithriskofCAD.Byanalyzingall commonSNPsinGATA2,twotagSNPswereidentified,includingrs2713604and rs2335052.Then,acase-controlassociationstudydesignwasusedtodeterminewhether SNPs rs2713604 and rs2335052 we associated with CAD.Forrs2713604, 1120CADpatients and1116controls without CAD(all ofHan ethnic origin)weregenotypedandstatisticalanalysiswithPLINKandSPSSrevealedthat rs2713604 was not associated with CAD.Forrs2335052,1281CADpatientsand1316controlsweregenotyped.Allelic associationanalysiswithPLINKshowedthatrs2335052wasnotassociatedwithCAD (P=0.369).Genotypicassociationanalysis identifiedasignificant association between SNPrs2335052andCADinarecessiveinheritancemodel(P=0.013),buttheassociation becamenon-significantafteradjustingforCADriskfactors(P=0.756).Underadominant inheritancemodel,theassociationbetweenSNPrs2335052andCADwassignificantbeforeand after adjustment (observed P=1.01x10-6，adjusted P=0.014).ThedatainthisthesissuggestthatSNPrs2335052intheGATA2genemayconfera significantriskofCADinanantosomaldominantmodelintheChineseHanpopulation. These r