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ID:32818756
大小:2.45 MB
页数:50页
时间:2019-02-16
《fat10基因遗传变异与肝细胞癌发生发展的关联性研究》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、南昌大学硕士学位论文FAT10基因遗传变异与肝细胞癌发生发展的关联性研究姓名:袁荣发申请学位级别:硕士专业:外科学指导教师:邵江华201205摘要,目的:研究FATl0基因外显子和侧翼序列单核苷酸多态性(single-nucleotidepolymo印hism,SNP)与肝细胞癌发生和临床病理的关系。方法:收集254例肝癌病例和268例健康对照人群外周血标本,提取DNA,通过DNA直接测序分析方法,检测两组人群F.ATl0基因外显子和侧翼序列单核苷酸多态性。应用Haploview统计软件分析研究对象的连锁不平衡和单体型,并应用病例对照分析方法进行相关
2、性研究。结果:在病例组和对照组共检测到lO个SNPs。依据测序数据和遗传不平衡分析选择3个tagSNPs(.143A/G、+3476T/C和+3527T/C)进行关联分析和单体型构建,发现.143A/G和+3476T/C基因型与相应的野生型纯合子相比明显降低肝癌的发病风险(OR=O.38,95%CI:0.22.O.66和OR=O.34,95%CI:0.21.O.56,p<0.05),但这些多态性位点的基因型频率与肝癌的临床表型无关(p>0.05)。另外单体型分析发现ATT、ATC、GCT和ACT四种单体型,其中肝癌组GCT和ACT单体型频率显著低于对
3、照组(OR=0.4l,95%CI=0.24.0.70和OR=O.43,95%CI=O.22.0.98,p<0.05),而ATT单体型频率显著高于对照组(OR=1.64,95%CI=1.24.2.17,p<0.05),经过l×108的随机置换检验校正后,ATT和GCT单体型与肝癌的发病风险仍然显著相关(p4、lO基因;单核苷酸多态性;单体型;肝细胞癌;病例对照研究AbstractABSTRACTobjectiVes:Thisstudyex帅inedwhethersinglenucleotidepolymorphisminexonicandflankingsequenceofthehumanHLA—Fadjacenttranscriptl0(FAT1O)genewereassociatedwithsusceptibiIityandclinicopathoIogicaldeVelopmentofhapatocellularcarcinoma(HCC).Met5、hods:Atotalof522suboects,including268healthycontrolsand254patientswithHCC,wererecruited.GenotypingwasdonebyusingDNAsequencing.HaplotypesandLinkagedisequ.1ibriumanalysiswereestimatedbyhaploViewsoRware.Theoddsratios(ORs)and95%con矗denceintervals(CIs)werecalcuIatedusingunconditiona6、llogisticregressionmodeltoestimatethecorrelationsoftheFATl0geneticVariationtodeVelopmentofhepatoceIlularcarcinoma.I沁sults:T色nSNPsinFATl0wereidentif.edinbothHCCpatientsandcontrolsubjects.The—143A/G+3476T/C,+3527T/CtagSNPsthatwereselectedforassociationandhaplotypeanalysiswerechos7、enbasedonthedataofDNAsequencingandlinkagedisequilibriumanalysis.The一143A/G+3476’r/CgenotypeswereassociatedwithadecreasedriskforHCC(OR=0.38,95%CI:0.22-0.66andOR=O.34,95%CI:0.2l-O.56,p0.05).Furthernlore,atotalo8、f4haplotypeswerefound,nameIyATT,ATC,GCT,ACT.thef-reque
4、lO基因;单核苷酸多态性;单体型;肝细胞癌;病例对照研究AbstractABSTRACTobjectiVes:Thisstudyex帅inedwhethersinglenucleotidepolymorphisminexonicandflankingsequenceofthehumanHLA—Fadjacenttranscriptl0(FAT1O)genewereassociatedwithsusceptibiIityandclinicopathoIogicaldeVelopmentofhapatocellularcarcinoma(HCC).Met
5、hods:Atotalof522suboects,including268healthycontrolsand254patientswithHCC,wererecruited.GenotypingwasdonebyusingDNAsequencing.HaplotypesandLinkagedisequ.1ibriumanalysiswereestimatedbyhaploViewsoRware.Theoddsratios(ORs)and95%con矗denceintervals(CIs)werecalcuIatedusingunconditiona
6、llogisticregressionmodeltoestimatethecorrelationsoftheFATl0geneticVariationtodeVelopmentofhepatoceIlularcarcinoma.I沁sults:T色nSNPsinFATl0wereidentif.edinbothHCCpatientsandcontrolsubjects.The—143A/G+3476T/C,+3527T/CtagSNPsthatwereselectedforassociationandhaplotypeanalysiswerechos
7、enbasedonthedataofDNAsequencingandlinkagedisequilibriumanalysis.The一143A/G+3476’r/CgenotypeswereassociatedwithadecreasedriskforHCC(OR=0.38,95%CI:0.22-0.66andOR=O.34,95%CI:0.2l-O.56,p0.05).Furthernlore,atotalo
8、f4haplotypeswerefound,nameIyATT,ATC,GCT,ACT.thef-reque
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