Effects of 16 Genetic Variants on Fasting Glucose and Type 2 Diabetes in South Asians ADCY5 and GLIS3 Variants May Predispose to Type 2 Diabetes 英文参考文献.docVIP

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Effects of 16 Genetic Variants on Fasting Glucose and Type 2 Diabetes in South Asians ADCY5 and GLIS3 Variants May Predispose to Type 2 Diabetes 英文参考文献.doc

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Effects of 16 Genetic Variants on Fasting Glucose and Type 2 Diabetes in South Asians ADCY5 and GLIS3 Variants May Predispose to Type 2 Diabetes 英文参考文献

Effectsof16GeneticVariantsonFastingGlucoseand Type2DiabetesinSouthAsians:ADCY5andGLIS3 VariantsMayPredisposetoType2Diabetes SimonD.Rees1,5*,M.ZafarI.Hydrie2,J.PaulO’Hare3,SudheshKumar3,A.SamadShera4,AbdulBasit2, AnthonyH.Barnett1,5,M.AnnKelly1,5 1CollegeofMedicalandDentalSciences,UniversityofBirmingham,Birmingham,UnitedKingdom,2BaqaiInstituteofDiabetologyandEndocrinology,Karachi,Pakistan, 3WarwickMedicalSchool,UniversityofWarwick,Coventry,UnitedKingdom,4DiabeticAssociationofPakistan,Karachi,Pakistan,5BioMedicalResearchCentre,Heartof EnglandNHSFoundationTrust,Birmingham,UnitedKingdom Abstract Background:TheMeta-AnalysisofGlucoseandInsulinrelatedtraitsConsortium(MAGIC)recentlyidentified16locirobustly associatedwithfastingglucose,someofwhichwerealsoassociatedwithtype2diabetes.Thepurposeofourstudywasto explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the DistrictofMirpur,Pakistan. Methodology/PrincipalFindings:Sixteensinglenucleotidepolymorphisms(SNPs)weregenotypedin1678subjectswith type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenoustotheDistrictofMirpur.Inthenormoglycaemiccontrolsinvestigatedforfastingglucoseassociations,12of16 SNPs displayed b values with the same direction of effect as that seen in European studies, although only the SLC30A8 rNPwasnominallyassociatedwithfastingglucose(b=0.063[95%CI:0.013,0.113]p=0.015).Ofinterest,the MTNR1BrNPdisplayedanegativebvalueforfastingglucoseinourstudy;thiseffectsizewassignificantlylower thanthatseeninEuropeans(p=1.2961024).Inadditiontopreviouslyreportedtype2diabetesriskvariantsinTCF7L2and SLC30A8,SNPsinADCY5(randGLIS3(rs7034200)displayedevidenceforassociationwithtype2diabetes,with oddsratiosof1.23(95%CI:1.09,1.39;p=9.161024)and1.16(95%CI:1.05,1.29;p=3.4961023 )respectively. Conclusions/Significance:AlthoughonlytheSLC30A8rNPwasnominallyassociatedwithfa