Risk Alleles of USF1 Gene Predict Cardiovascular Disease of Women in Two Prospective Studies 英文参考文献.docVIP

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Risk Alleles of USF1 Gene Predict Cardiovascular Disease of Women in Two Prospective Studies 英文参考文献.doc

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Risk Alleles of USF1 Gene Predict Cardiovascular Disease of Women in Two Prospective Studies 英文参考文献

RiskAllelesofUSF1GenePredict CardiovascularDiseaseofWomeninTwo ProspectiveStudies Kati Komulainen1,Mervi Alanne1[,Kirsi Auro1[,Riika Kilpikari1,Pa¨iviPajukanta2,Janna Saarela1,Pekka Ellonen1, Kaisa Salminen3,Sangita Kulathinal3,Kari Kuulasmaa3,Kaisa Silander1,Veikko Salomaa3,Markus Perola1,4, Leena Peltonen1,4,5* 1DepartmentofMolecularMedicine,NationalPublicHealthInstitute,Biomedicum,Helsinki,Finland,2DepartmentofHumanGenetics,DavidGeffenSchoolofMedicineat UCLA,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,3DepartmentofEpidemiologyandHealthPromotion,NationalPublicHealth Institute,Helsinki,Finland,4DepartmentofMedicalGenetics,UniversityofHelsinki,Helsinki,Finland,5TheBroadInstitute,MassachusettsInstituteofTechnology,Boston, Massachusetts,UnitedStatesofAmerica Upstreamtranscriptionfactor1(USF1)isaubiquitouslyexpressedtranscriptionfactorcontrollingseveralcriticalgenes in lipid and glucose metabolism. Of some 40 genes regulated by USF1, several are involved in the molecular pathogenesisofcardiovasculardisease(CVD).AlthoughtheUSF1genehasbeenshowntohaveacriticalroleinthe etiologyoffamilialcombinedhyperlipidemia,whichpredisposestoearlyCVD,thegene’spotentialroleasariskfactor forCVDeventsatthepopulationlevelhasnotbeenestablished.Herewereporttheresultsfromaprospectivegenetic– epidemiologicalstudyoftheassociationbetweentheUSF1variants,CVD,andmortalityintwolargeFinnishcohorts. Haplotype-taggingsinglenucleotidepolymorphismsexposingallcommonallelicvariantsofUSF1weregenotypedina prospective case-cohort design with two distinct cohorts followed up during 1992–2001 and 1997–2003. The total numberoffollow-upyearswas112,435in14,140individuals,ofwhich2,225wereselectedforgenotypingbasedon thecase-cohortstudystrategy.Afteradjustmentforconventionalriskfactors,weobservedanassociationofUSF1with CVDandmortalityamongfemales.Incombinedanalysisofthetwocohorts,femalecarriersofaUSF1riskhaplotype had a 2-fold risk of a CVD event (hazard ratio [HR] 2.02; 95% co