Effects of Genetic Variants in ADCY5, GIPR, GCKR and VPS13C on Early Impairment of Glucose and Insulin Metabolism in Children 英文参考文献.docVIP

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Effects of Genetic Variants in ADCY5, GIPR, GCKR and VPS13C on Early Impairment of Glucose and Insulin Metabolism in Children 英文参考文献.doc

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Effects of Genetic Variants in ADCY5, GIPR, GCKR and VPS13C on Early Impairment of Glucose and Insulin Metabolism in Children 英文参考文献

EffectsofGeneticVariantsinADCY5,GIPR,GCKRand VPS13ConEarlyImpairmentofGlucoseandInsulin MetabolisminChildren JanWindholz1.,PeterKovacs2*.,AnkeTo¨njes3,4,KathrinDittrich1,SusannBlu¨her1,4,WielandKiess1, MichaelStumvoll3,4,AntjeKo¨rner1,4 1UniversityHospitalforChildrenandAdolescents,UniversityofLeipzig,Leipzig,Germany,2InterdisciplinaryCenterforClinicalResearch,UniversityofLeipzig,Leipzig, Germany,3DepartmentofMedicine,UniversityofLeipzig,Leipzig,Germany,4LeipzigUniversityMedicalCenter,IFBAdiposityDiseases,UniversityofLeipzig,Leipzig, Germany Abstract Objective:Recentgenome-wideassociationstudiesidentifiednovelcandidategenesforfastingand2hbloodglucoseand insulinlevelsinadults.Weinvestigatedtheroleoffouroftheseloci(ADCY5,GIPR,GCKRandVPS13C)inearlyimpairmentof glucoseandinsulinmetabolisminchildren. Research Design and Methods: We genotyped four variants (rs2877716; rs1260326; r r in 638 CaucasianchildrenwithdetailedmetabolictestingincludinganoGTTandassessedassociationswithmeasuresofglucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regressionanalysesadjustedforage,sex,BMI-SDSandpubertalstage. Results: Themajorallele(C)ofrs2877716(ADCY5)wasnominallyassociatedwithdecreasedfastingplasmainsulin(P=0.008), peakinsulin(P=0.009)andincreasedQUICKI(P=0.016)andMatsudainsulinsensitivityindex(P=0.013).rVPS13C )was nominallyassociatedwith2hbloodglucose(P=0.009),butnotwithanyoftheinsulinorinsulinsensitivityparameters.Wefound noassociationoftheGIPRandGCKRvariantswithparametersofglucoseandinsulinmetabolism.Noneofthevariantscorrelated withanthropometrictraitssuchasheight,WHRorBMI-SDS,whichexcludedpotentialunderlyingassociationswithobesity. Conclusions:OurdataonobesechildrenindicateeffectsofgeneticvariationwithinADCY5inearlyimpairmentofinsulin metabolismandVPS13Cinearlyimpairmentofbloodglucosehomeostasis. Citation:WindholzJ,KovacsP,To¨njesA,DittrichK,Blu¨herS,etal.(2011)Effect