Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk A Fine-Mapping Study in Chinese Population 英文参考文献.docVIP

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Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk A Fine-Mapping Study in Chinese Population 英文参考文献.doc

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Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk A Fine-Mapping Study in Chinese Population 英文参考文献

GeneticVariantsofIDE-KIF11-HHEXat10q23.33 AssociatedwithType2DiabetesRisk:AFine-Mapping StudyinChinesePopulation YunQian1,2*,FengLu1,MeihuaDong2,YudiLin2,HuizhangLi1,JianChen2,ChongShen1,GuangfuJin1, ZhibinHu1,HongbingShen1* 1DepartmentofEpidemiologyandBiostatistics,SchoolofPublicHealth,NanjingMedicalUniversity,Nanjing,China,2DepartmentofChronicNon-communicableDisease Control,WuxiCenterforDiseaseControlandPrevention,Wuxi,China Abstract Background:Genome-wideassociationstudies(GWAS)inpopulationsofEuropeanancestryhavemappedatype2diabetes susceptibilityregiontochromosome10q23.33containingIDE,KIF11andHHEXgenes(IDE-KIF11-HHEX),whichhasalsobeen replicatedinChinesepopulations.However,thefunctionalrelevanceforgeneticvariantsatthislocusisstillunclear.Itis criticaltosystematicallyassesstherelationshipofgeneticvariantsinthisregionwiththeriskoftype2diabetes. Methodology/PrincipalFindings:Afine-mappingstudywasconductedbygenotypingfourteentaggingsingle-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetesinaChineseHanpopulation.Suggestiveassociations(P,0.05)observedfrom1,200casesand1,200controlsinthe first stage were further replicated in 1,725 cases and 2,081 controls in the second stage. Seven tagging SNPs were consistentlyassociatedwithtype2diabetesinbothstages(P,0.05),withcombinedoddsratios(ORs)rangingfrom1.14to 1.33inthecombinedanalysis.Themostsignificantlocuswasrs7923837[OR=1.33,95%confidenceinterval(CI):1.21–1.47] atthe39-flankingregionofHHEXgene.SNPrs1111875wasfoundtobeanotherpartiallyindependentlocus(OR=1.23,95% CI:1.13–1.35)inthisregionthatwasassociatedwithtype2diabetesrisk.Acumulativeeffectofrs7923837andrs1111875 was observed with individuals carrying 1, 2, and 3 or 4 risk alleles having a 1.27, 1.44, and 1.73-fold increased risk, respectively,fortype2diabetes(Pfortrend=4.1E-10). Conclusions/Significance:OurresultsconfirmthatgeneticvariantsoftheIDE-KIF11-HHEXregionat10q23.33contributeto