年龄相关性皮质性白内障波形蛋白基因外显子和启动子的研究

发布时间：2018-12-12 16:03

【摘要】：目的:探讨波形蛋白基因(Vimentin)外显子和启动子序列(包括链接外显子和启动子的5'非翻译区,5'UTR)与中国汉族人群年龄相关性皮质性白内障的关系。方法:选择年龄相关性皮质性白内障患者138例(病例组)及同一地区正常对照133例(对照组)进行以医院病例资料为基础的对照研究。以外周血基因组DNA为模板,通过聚合酶链反应(Polymerase Chain Reaction, PCR)扩增Vimentin基因外显子、5'UTR以及启动子,并将PCR产物纯化后测序。测序结果与GenBank公布的Vimentin基因正常序列比对。所有受试对象均对六种单核苷酸多态性(single nucleotide polymorphisms, SNPs),分别是:VIM:rs3758410(VIM:g. 17271400GC)、VIM:g. 17271110GC、VIM:g. 17270912AG、VIM:rs17140300(VIM:g. 17269762AG)、VIM:g. 17268954CG和VIM:g. 17268834TC进行基因分型分析。基因分型和单倍体表型采用卡方检验进行分析。结果:病例组和对照组,Vimentin基因全部外显子序列中,并未发现突变或是SNPs。病例组和对照组Vimentin基因5'UTR有两种SNPs具有显著性差异。VIM:rs3758410(VIM:g. 17271400GC)等位基因频率在年龄相关性皮质性白内障组中显著高于正常对照组(P =0.0001, OR: 2.208)。VIM:g. 17271110GC基因分型频率在年龄相关性皮质性白内障组高于正常对照组(P =0.04, OR: 1.591)。VIM:g. 17270912G和VIM:g.17271110C-22G的单倍型与年龄相关性皮质性白内障呈强相关性(P=0.008, OR: 8.185)。两组Vimentin基因启动子序列中发现三种SNPs,分别是:VIM:rs17140300(VIM:g. 17269762AG)、VIM:g. 17268954CG和VIM:g. 17268834TC。暂时未发现此三种SNPs与年龄相关性皮质性白内障相关(P 0.05)。结论:中国汉族人群年龄相关性皮质性白内障的发病与Vimentin基因外显子无关。本研究首次发现Vimentin基因与中国汉族人群年龄相关性皮质性白内障相关的新的SNPs,即VIM:g. 17271110GC、VIM:g. 17270912AG、VIM:g. 17268954CG和VIM:g. 17268834TC。本研究首次在年龄相关性皮质性白内障中发现VIM:rs3758410(VIM:g. 17271400GC)和VIM:rs17140300(VIM:g. 17269762AG)。VIM:g. 17270912G和17271110C-22G是中国汉族人群年龄相关性皮质性白内障的候选单倍型。
[Abstract]:Aim: to investigate the relationship between the vimentin gene (Vimentin) exon and promoter sequence (including 5'untranslated region (5'UTR) linked to exon and promoter) and age-related cortical cataract in Chinese Han population. Methods: 138 cases of age-related cortical cataract (case group) and 133 cases of normal control (control group) were studied. The exon, 5'UTR and promoter of Vimentin gene were amplified by polymerase chain reaction (Polymerase Chain Reaction, PCR) using genomic DNA of peripheral blood as template. The PCR product was purified and sequenced. The sequencing results were compared with the normal sequence of Vimentin gene published by GenBank. The six single nucleotide polymorphisms (SNP) (single nucleotide polymorphisms, SNPs), of all subjects were: VIM:rs3758410 (VIM:g.) 17271400GC), VIM:g. 17271110GC,VIM:g. 17270912 AGI: rs17140300 (VIM:g. 17269762AG), VIM:g. 17268954CG and VIM:g. 17268834TC genotyping was performed. Genotyping and haploid phenotypes were analyzed by chi-square test. Results: no mutation or SNPs. was found in all exons of Vimentin gene in case group and control group. There was a significant difference between the two SNPs types of Vimentin gene 5'UTR between the case group and the control group. VIM:rs3758410 (VIM:g.) 17271400GC) allele frequency in age-related cortical cataract group was significantly higher than that in normal control group (P = 0.0001, OR: 2.208). VIM:g. The frequency of 17271110GC genotyping in age-related cortical cataract group was higher than that in normal control group (P = 0.04, OR: 1.591). VIM:g. Haplotypes of 17270912 G and VIM:g.17271110C-22G were strongly correlated with age-related cortical cataract (P0. 008, OR: 8.185). Three kinds of SNPs, were found in two groups of Vimentin gene promoters: VIM:rs17140300 (VIM:g.) 17269762AG), VIM:g. 17268954CG and VIM:g. 17268834TC. These three SNPs were not found to be associated with age-related cortical cataract (P 0. 05). Conclusion: age-related cortical cataract is not related to the exon of Vimentin gene in Chinese Han population. In this study, we first found a new SNPs, of Vimentin gene associated with age-related cortical cataract in Chinese Han population, that is, VIM:g.. 17271110GC,VIM:g. 17270912AG,VIM:g. 17268954CG and VIM:g. 17268834TC. VIM:rs3758410 (VIM:g.) was first found in age-related cortical cataract in this study. 17271400GC) and VIM:rs17140300 (VIM:g.) 17269762AG) 17270912 G and 17271110C-22G are candidate haplotypes for age-related cortical cataract in Chinese Han population.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R776.1

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