Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals 英文参考文献.docVIP

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Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals 英文参考文献.doc

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Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals 英文参考文献

AlleleSummationofDiabetesRiskGenesPredicts ImpairedGlucoseToleranceinFemaleandObese Individuals KatarzynaLinder1.,RobertWagner1.,ErifiliHatziagelaki2,CarolineKetterer1,MartinHeni1, FaustoMachicao1,NorbertStefan1,HaraldStaiger1,Hans-UlrichHa¨ring1,AndreasFritsche1,3* 1Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, Eberhard Karls University Tu¨bingen, Member of the German Centre for Diabetes Research, Tu¨bingen, Germany, 22nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens UniversityMedicalSchool,‘‘Attikon’’UniversityHospital,Athens,Greece,3DepartmentofInternalMedicine,DivisionofNutritionalandPreventiveMedicine,University HospitalTu¨bingen,Tu¨bingen,Germany Abstract Introduction:Singlenucleotidepolymorphisms(SNPs)inapproximately40geneshavebeenassociatedwithanincreased riskfortype2diabetes(T2D)ingenome-wideassociationstudies.Itisnotknownwhetherasimilargeneticimpactonthe riskofprediabetes(impairedglucosetolerance[IGT]orimpairedfastingglycemia[IFG])exists. Methods:Inourcohortof1442non-diabeticsubjectsofEuropeanorigin(normalglucosetolerance[NGT]n=1046,isolated IFGn=142,isolatedIGTn=140,IFG+IGTn=114),animpactonglucosehomeostasishasbeenshownfor9SNPsinprevious studiesinthisspecificcohort.WeanalyzedtheseSNPs(withinorinthevicinityofthegenesTCF7L2,KCNJ11,HHEX,SLC30A8, WFS1,KCNQ1,MTNR1B,FTO,PPARG)forassociationwithprediabetes. Results:ThegeneticriskloadwassignificantlyassociatedwiththeriskforIGT(p=0.0006)inamodelincludinggender,age, BMIandinsulinsensitivity.Tofurtherevaluatepotentialconfoundingeffects,westratifiedthepopulationongender,BMI andinsulinsensitivity.TheassociationoftheriskscorewithIGTwaspresentinfemaleparticipants(p=0.008),butnotin maleparticipants.TheriskscorewassignificantlyassociatedwithIGT(p=0.008)insubjectswithabodymassindexhigher than 30kg/m2 but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association be