Single Nucleotide Polymorphisms of TCF7L2 Are Linked to Diabetic Coronary Atherosclerosis 英文参考文献.docVIP

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Single Nucleotide Polymorphisms of TCF7L2 Are Linked to Diabetic Coronary Atherosclerosis 英文参考文献.doc

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Single Nucleotide Polymorphisms of TCF7L2 Are Linked to Diabetic Coronary Atherosclerosis 英文参考文献

SingleNucleotidePolymorphismsofTCF7L2AreLinked toDiabeticCoronaryAtherosclerosis AxelMuendlein1,2,ChristophH.Saely1,2,3,SimoneGeller-Rhomberg1,2,GudrunSonderegger1, PhilippRein1,2,3,ThomasWinder1,2,3,StefanBeer1,2,3,AlexanderVonbank1,2,3,HeinzDrexel1,2,3,4 * 1Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria, 2Private University of the Principality of Liechtenstein, Triesen, Principality of Liechtenstein,3DepartmentofMedicineandCardiology,AcademicTeachingHospitalFeldkirch,Feldkirch,Austria,4DrexelUniversityCollegeofMedicine,Philadelphia, Pennsylvania,UnitedStatesofAmerica Abstract Background: Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variantsoftheTCF7L2locusandcoronaryatherosclerosisareuncertain.Wethereforeinvestigatedtheassociationbetween TCF7L2polymorphismsandangiographicallydeterminedCADindiabeticandnon-diabeticpatients. Methodology/Principal Findings: We genotyped TCF7L2 variants rs7903146, r and rin a cross- sectionalstudyincluding1,650consecutivepatientsundergoingcoronaryangiographyfortheevaluationofestablishedor suspectedstableCAD.SignificantCADwasdiagnosedinthepresenceofcoronarystenoses$50%.Variantrs7903146inthe totalstudycohortwassignificantlyassociatedwithsignificantCAD(adjustedadditiveOR=1.29[1.09–1.53];p=0.003).This associationwasstrongandsignificantinT2DMpatients(n=393;OR=1.91[1.32–2.75];p=0.001)butnotinnon-diabetic subjects(OR=1.09[0.90–1.33];p=0.370).TheinteractionriskallelebyT2DMwassignificant(pinteraction=0.002),indicatinga significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rand rwere also significantly associated with CAD in diabetic patients (adjusted additive OR=1.90 [1.31–2.74]; p=0.001 and OR=1.75 [1.22–2.50]; p=0.002