Polymorphism rs11085226 in the Gene Encoding Polypyrimidine Tract-Binding Protein 1 Negatively Affects Glucose-Stimulated Insulin Secretion 英文参考文献.docVIP

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Polymorphism rs11085226 in the Gene Encoding Polypyrimidine Tract-Binding Protein 1 Negatively Affects Glucose-Stimulated Insulin Secretion 英文参考文献.doc

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Polymorphism rs11085226 in the Gene Encoding Polypyrimidine Tract-Binding Protein 1 Negatively Affects Glucose-Stimulated Insulin Secretion 英文参考文献

PolymorphismrntheGeneEncoding PolypyrimidineTract-BindingProtein1Negatively AffectsGlucose-StimulatedInsulinSecretion MartinHeni1,CarolineKetterer1,RobertWagner1,KatarzynaLinder1,AnjaBo¨hm1,SilkeA.Herzberg- Scha¨fer1,FaustoMachicao1,2,Klaus-PeterKnoch4,AndreasFritsche1,2,3,HaraldStaiger1,2 ,Hans- UlrichHa¨ring1,2*,MicheleSolimena4 1DivisionofEndocrinology,Diabetology,Angiology,NephrologyandClinicalChemistry,DepartmentofInternalMedicine,EberhardKarlsUniversityTu¨bingen,Tu¨bingen, Germany, 2Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tu¨bingen, Partner in the German Center for DiabetesResearch(DZD),Tu¨bingen,Germany,3DepartmentofInternalMedicine,NutritionalandPreventiveMedicine,EberhardKarlsUniversityTu¨bingen,Tu¨bingen, Germany, 4Molecular Diabetology, Paul Langerhans Institute Dresden, University Hospital and Medical School Carl Gustav Carus, Dresden University of Technology, PartnerintheGermanCenterforDiabetesResearch(DZD),Dresden,Germany Abstract Objective:Polypyrimidinetract-bindingprotein1(PTBP1)promotesstabilityandtranslationofmRNAscodingforinsulin secretion granule proteins and thereby plays a role in b-cells function. We studied whether common genetic variations withinthePTBP1locusinfluenceinsulinsecretion,and/orproinsulinconversion. Methods:Wegenotyped1,502healthyGermansubjectsforfourtaggingsinglenucleotidepolymorphisms(SNPs)within the PTBP1 locus (rs351974, r rs736926, and rs123698) covering 100%of genetic variation with anr2$0.8. The subjects were metabolically characterized by an oral glucose tolerance test with insulin, proinsulin, and C-peptide measurements.Asubgroupof320subjectsalsounderwentanIVGTT. Results:PTBP1SNPrasnominallyassociatedwithlowerinsulinogenicindexandlowerclearedinsulinresponse in the OGTT (p#0.04). The other tested SNPs did not show any association with the analyzed OGTT-derived secretion parameters.IntheIVGTTsubgroup,SNPrasaccordin