Polymorphisms in the Presumptive Promoter Region of the SLC2A9 Gene Are Associated with Gout in a Chinese Male Population 英文参考文献.docVIP

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Polymorphisms in the Presumptive Promoter Region of the SLC2A9 Gene Are Associated with Gout in a Chinese Male Population 英文参考文献.doc

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Polymorphisms in the Presumptive Promoter Region of the SLC2A9 Gene Are Associated with Gout in a Chinese Male Population 英文参考文献

PolymorphismsinthePresumptivePromoterRegionof theSLC2A9GeneAreAssociatedwithGoutinaChinese MalePopulation ChangguiLi1*.,NanChu1.,BinbinWang2,3,JingWang2,3,JianLuan4,LinHan1,DongmeiMeng1, YunlongWang1,PeisuSuo2,3,LongfeiCheng2,3,XuMa2,3,5,ZhiminMiao1,ShiguoLiu1* 1TheAffiliatedHospitalofMedicalCollege,QingdaoUniversity,Qingdao,China,2Graduateschool,PekingUnionMedicalCollege,Beijing,China,3NationalResearch Institute for Family Planning,Beijing, China, 4QingdaoMunicipalHospital,Qingdao,China, 5World Health Organization Collaborating Centre for Research in Human Reproduction,Beijing,China Abstract Background: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wideassociationstudies(GWAS)andfollow-upstudieshaveidentifiedgeneticvariantsofSLC2A9associatedwith urateconcentrationsandsusceptibilitytogout.Wethereforeinvestigatedassociationsbetweengoutandpolymorphisms andhaplotypesinthepresumptivepromoterregionofGLUT9inChinesemales. Methodology/PrincipalFindings:Theapproximately2000bppresumptivepromoterregionupstreamofthestartsiteof exon1ofGLUT9wassequencedandsubjectedtogeneticanalysis.Agenotype-phenotypecorrelationwasperformedand polymorphisms-inducedchangesintranscriptionfactorbindingsiteswerepredicted.Of21SNPsidentifiedinGLUT9 ,five hadnotbeenpreviouslyreported.TwooftheSNPs(rndrs6850166)wereassociatedwithsusceptibilitytogout (p=0.009andp=0.042,respectively).TheCalleleofrppearedtobetheriskalleleforpredispositiontogout (p=0.006, OR 1.709 [95% CI 1.162–2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p=0.029,OR1.645[95%CI1.050–2.577]).AfterBonferronicorrection,therewasstatisticallydifferenceinrllele frequenciesbetweengoutcasesandcontrols(P=0.042).HaplotypeanalysesshowedthathaplotypeGGwasaprotective haplotype (p=0.0053) and haplotype CA was associated with increased risk of gout (p=0.0326). Genotype-phenotype analysisamonggoutpatientsrevealedanassociati