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
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
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