阿尔兹海默病患者线粒体转运RNA变异的初步研究  

The preliminary study of mitochondrial transfer RNA variants in patients with Alzheimer's disease

作　　者：袁妮娜 章瑜[1] 丁禹[1] 冷建杭[1] Yuan Nina

机构地区：[1]杭州市第一人民医院,310006

出　　处：《浙江临床医学》2021年第12期1724-1726,共3页Zhejiang Clinical Medical Journal

摘　　要：目的探讨线粒体转运RNA基因多态性与阿尔兹海默病(AD)的相关性。方法提取100例AD患者和50例健康对照个体的外周血基因组DNA,PCR扩增22个线粒体tRNA基因并测序,测序结果与线粒体标准序列进行比对,使用DNA STAR软件鉴定多态性位点,同时结合种系进化保守分析对变异位点进行分析,筛选致病性突变位点。结果PCR直接测序结果共发现5个突变位点,tRNA^(Ile)A4263G、tRNA^(Ala)T5655C、tRNA^(Cys)T5802C、tRNA^(Glu)A14693G以及tRNA^(Thr)G15927A,但是这些变异位点在健康对照组中未发现。进一步的研究发现,A4263G、T5655C、T5802C、A14693G和G15927A变异在进化上高度保守,推测这些变异位点可能引起线粒体tRNA代谢障碍,导致线粒体呼吸链功能受损,引起线粒体功能损伤,进而参与AD的发病进程。结论线粒体tRNA^(Ile)A4263G、tRNA^(Ala)T5655C、tRNA^(Cys)T5802C、tRNA^(Glu)A14693G以及tRNA^(Thr)G15927A突变与AD有关,可为AD的早期诊断及预警提供理论依据。Objective To explore the potential association between mitochondrial transfer RNA variants and Alzheimer's disease.Methods Extract the genomic DNA from 100 patients with Alzheimer's disease and 50 healthy subjects,then we performed the PCR amplification of 22 mitochondrial tRNA genes,the PCR products were sequenced and the variants were detected by DNA STAR software.Moreover,the phylogenetic approach was used to analysis the potential pathogenic mitochondrial tRNA mutations.Results PCR direct sequencing suggested the presence of five mutations,tRNA^(Ile)A4263G,tRNA^(Ala)T5655C,tRNA^(Cys)T5802C,tRNA^(Glu)A14693G and tRNA^(Thr)G15927A,but these mutations were absent in control subjects.Phylogenetic analysis revealed that these mutations were localized at very conserved nucleotide of the corresponding tRNAs and might result the failure in tRNA metabolism,which might subsequently lead to the impairment of mitochondrial respiratory chain function,these events would result in mitochondrial dysfunction and involve in the pathogenesis and progression of Alzheimer's disease.Conclusion Mitochondrial tRNA^(Ile)A4263G,tRNA^(Alu)T5655C,tRNA^(Cys)T5802C,tRNA^(Glu)A14693G and tRNA^(Thr)G15927A mutations are associated with Alzheimer’s disease,our study provides useful information for the early diagnosis and prevention of this disease.

关 键 词：阿尔兹海默病 线粒体转运RNA 变异 相关性 

分 类 号：R73[医药卫生—肿瘤]