CD40-1CT多态性rs1883832与粤西汉族人Graves病的关系.docx

CD40-lCf多态性(rs)与粤西汉族人GraVeS病的关系陈晓铭胡卓清李潍刘美莲吴美芬方烁武革【摘要】目的探讨CD40基因单核甘酸多态性(rs)与粤西汉族人群GraVeS病的关系。方法选取Graves病患者219例(GraVeS病组)和健康体检人员200例(对照组)。收集相关资料，检测甲状腺激素(游离T3、游离T4)、促甲状腺激素(TSH)及促甲状腺激素受体抗体(TRAb)水平。应用聚合酹链反应限制性片段长度多态性(PCRRFLP)对样本基因分型。分析基因多态性与GraVeS病遗传易感性、家族史、眼病和预后的关系，及TRAb水平在不同基因型携带者之间的差异。结果(1)Graves病组等位基因C分布频率高于对照组(56.8%vs.47.3%,2=7.722,P=0.005);共性及隐性遗传模型均显示GraVeS病组CC基因型高于对照组(38.4%vs.25.5%,%2=8.054共性=0.018次2=7.9121隐性=0.005)；相对于等位基因T携带者，CC基因型增加GraVeS病发病风险CCvs.TT：优势比(OR)=1.89,CCvs.CT：OR=1.77,CCvs.CT+TT：OR=1.83)<,(2)等位基因与基因型分布频率在有/无家族史、伴/不伴眼病及初发/复发亚组中差异均无统计学意义(P均>0.05)。(3)在Graves病组中，C等位基因携带者TRAb水平较TT基因型者高(18.23±0.96)vs.(12.65±1.68)IUL,F=4.576,P=0.002o结论CD40-1C/T多态性(rs)可能与粤西汉族人群GraVeS病及TRAb水平相关，与甲状腺眼病、家族史及预后无关。【关键词】GmVeS病；CD40；基因多态性DOI：10.3760cma.j.issn.l6734157.2015.01.003基金项目:广东省社会发展领域科技计划项目(2012B)；广东省医学科研基金立项课题(A)；湛江市非资助科技攻关计划项目(2013B01030)作者单位：524001湛江，广东医学院附属医院内分泌科通信作者：武革，Email:RelationshipbetweenCD401CTpolymorphism(rs)andGraves*diseaseofHanpopulationinwesternregionofGuangdongprovinceChenXiaoming,HuZhuoqing,LiWei,LiuMeilian,WuMeifen,FangShuo,WuGe.DepartmentofEndocrinology,AffiIiatedHospitalofGuangdongMedicalCollege,Zhanjiang524001,ChinaCorrespondingauthor:WuGe,Email:【AbstractObjectiveToinvestigatetheassociationbetweenthesinglenucleotidepolymorphism(SNP,rs)ofCD40geneandGraves,disease(GD)ofHanpopulationinwesternGuangdong.MethodsAsetofsubjectsincluding219patientswithGD(GDgroup)and200healthycontrols(controlgroup)wereedinformationswerecollected,andlevelsofthyroidhormones(freeT3,freeT4),thyroidstimulatinghormone(TSH)andthyrotropinreceptorantibodies(TRAb)weretested.SNPsweregenotypedbythemethodofpolymerasechainreactionrestrictionfragmentlengthpolymorphism(PCR-RFLP).TheassociationbetweenpolymorphismandthesusceptibilityofGD,familyhistory,ophthalmopathyandprognosisofGDwerehile,thelevelsofTRAbamongdifferentgenotypeswerecompared.Results(1)HigheralleleCfrequencywasobservedinGDgroupthancontrolgroup(56.8%vs.47.3%,2=7.722,P=0.005).Comparcdwithcontrolgroup,additiveandrecessivegeneticmodelsshowedthefrequencyofCCgenotypewerehigherinGDgroup(38.4%vs.25.5%,2=8.054,PAdditive=O,018;%2=7.912,PRessive=0.005).ComparedwithpatientscarriedalleleT,GDriskoftheindividualswhocarriedCCgenotypewassignificantlyincreasedCCvs.TToddratio(OR)=1.89,CCvs.CT:OR=1.77,CCvs.CT+TT:OR=L83.(2)TherewasnosignificantdifferenceinalleleorgenotypefrequencyofCD40SNPbetweenpatientswithandwithoutGDfamilyhistory,withandwithoutophthalmopathy,GDonsetandrelapsesubgroup(allP>0.05).(3)InGDgroup,thelevelsofTRAbweresignificanthigherinthosewithCCorCTgenotypethanothergenotype(18.23±0.96)vs.(12.65±1.68)UL,F=4.576,P=0.002.ConclusionCD40-1C/Tpolymorphism(rs)isassociatedwithGDandTRAblevelofHanpopulationinwesternGuangdong.NocorrelationisfoundbetweenCD4O-1CTpolymorphismandophthalmopathy,familyhistoryandprognosisofGD.KeywordsGraves*disease;CD40;Genepolymorphisms参考文献lBrixTH,KyvikKO,ChristensenK,etal.EvidenceforamajorroleofheredityinGraVeS'diseasespopulationbasedstudyoftwoDanishtwincohortsJ.JClinEndocrinolMetab,2001,86(2):930-934.2BalazsC.TheroleofhereditaryandenvironmentfactorsinautoimmunethyroiddiseaseJ.OrvHetil,2012,153(26):1013-1022.3JacobsonEM,HuberAK,AkenoN,etal.ACD40KozaksequencepolymorphismandsusceptibilitytoantibodymediatedautoimmuneConditionslheroleofCD40tissuespecificexpressionJ.GenesImmun,2007,8(3):205-214.吴砂.免疫细胞膜分子龚非力，主编.医学免疫学M.第3版.北京：科学出版t,2012:69-72.5YangJ,QinQ,YanN,etal.CD40CT(-1)andCTLA-4AG(49)SNPsareassociatedwithautoimmunethyroiddiseasesintheChinesepopulationJ.Endocrine,2012,41(1):111-115.王海宁，江鹤，刘威，等.在中国汉族人群中CD405，非翻译区的SNP与GraVeS病相关Il中华医学会第十二次全国内分泌学学术会议论文汇编，西安，2(H3C.2013419.7TomerY,BanY,ConcepcionG,etal.CommonanduniquesusceptibilitylociinGraves,andHashimotorSdisease:resultsofwholegenomescreeninginadatasetof102multiplexfamiliesJ.AmJHunGenet,2003,73(4):736-747.网滕卫平，甲状腺功能亢进症葛均波，徐永健，主编.内科学M.第8版.北京：人民卫生出版社,2013:685-692.9SmithTJ,SciakyD,PhippsRP,etal.CD40expressioninhumanthyroidtissue:evidenceforinvolvementofmultiplecelltypesinautoimmuneandneoplasticdiseasesJ.Thyoid,l999,9(8):749-755.10JacobsonEM,ConcepcionE,OashiT,etal.AGraves,diseaseassociatedKozaksequencesinglenucleotidepolymorphismenhancetheefficiencyofCD40genetranslation:acasefortranslationalpathophysiologyJ.Endocrinology,2005,146(6):2684-2691.11JHsiaoJY,TienKJ,HsiaoCT,etal.AC/TpolymorphisminCD40geneisnotassociatedwithsusceptibilityandphenotypeofGraves,diseaseinTaiwaneseJ.EndocrJ,2008,55(3):477-484.112孙玲玲，褚讯，黄薇，等.CD40基因多态性与Graves病的相关性研究J.实用医学杂志,2007,23(5):655-657.13马利丹，阎胜利，李等.CD40基因5,非翻译区-1位点CzT多态性与GraVeS病药物治疗停药后复发的相关性UL免疫学杂志,2010,26(6):517-520,526.14WangPW,ChenIY,JuoSH,etal.GenotypeandphenotypepredictorsofrelapseofGraves,diseaseafterantithyroiddrugwithdrawalJ.EurThyroidJ,20l33(4):251-258.15HuberAK,FinkelmanFD,LiCW,etal.GeneticallydriventargettissueoverexpressionofCD40:anovelmechanisminautoimmunediseaseJ.JImmunol,2012,189(6):3043-3053.（收稿口期：2014-07-14）