深圳地区2型糖尿病线粒体tRNA基因组突变分析  

Mutational analysis of mitochondrial t RNA genes in type 2 diabetes mellitus patients from Shenzhen area

作　　者：叶艺艺[1] 庄雄杰 桑丹[1] 蒋凤秀[1] 

机构地区：[1]中山大学附属第八医院内分泌科,深圳福田518033

出　　处：《中国优生与遗传杂志》2018年第2期25-28,12,共5页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨线粒体tRNA基因突变和深圳地区2型糖尿病之间的关系,为2型糖尿病的分子诊断提供理论依据。方法选取2015年1月到2017年1月在深圳市XX医院就诊的被诊断为2型糖尿病的患者300人,同时选取150例性别和年龄相仿的正常人群作为对照组,采用PCR扩增22个线粒体tRNA基因并进行测序分析,测序结果和线粒体的标准序列进行比对,确定突变位点并做相关性分析。结果在这些患者中,我们发现存在4个致病性的线粒体tRNA突变位点:tRNA^(Leu(UUR))A3243G,tRNA^(Met) A4435G,tRNA^(Glu) A14692G和tRNA^(Thr) G15927A,这些突变位于进化上高度保守的区域,可能会影响线粒体tRNA代谢,导致线粒体蛋白合成受阻,引起线粒体功能障碍,进而参与了2型糖尿病的发病进程。结论线粒体tRNA基因突变可能是2型糖尿病的重要发病基础,具有重要的临床意义。Objective：To investigate the association between mitochondrial tRNA mutations and type 2 diabetes mellitus（T2DM）,and provided the valuable information for molecular diagnosis of T2DM. Methods：Between January 2015 and January 2017,we recruited 300 T2DM patients and 150 healthy subjects with age-and gender-matched as controls from XX hospital. We first used PCR amplification of the 22 mitochondrial tRNA genes and subsequently sequenced the PCR products. Then we compared the sequences data with the mitochondrial genome to screen the potential pathogenic mutations. Results：Among these T2DM patients,we identified 4 potential pathogenic mutations：tRNA^（Leu（UUR））A3243G,tRNA^（Met） A4435G,tRNA^（Glu） A14692G and tRNA^（Thr） G15927A. These mutations were localized at the very conserved nucleotides of the corresponding tRNAs and may result the failure in mitochondrial tRNAs metabolism,subsequently cause the mitochondrial protein synthesis defects. Thus,it can be speculated that these mutations will cause mitochondrial dysfunction that is responsible for T2DM. Conclusions：Mitochondrial tRNA mutations may be the important causes for T2DM,which is of clinical significance.

关 键 词：2型糖尿病 线粒体tRNA基因 突变 深圳地区 

分 类 号：R587.1[医药卫生—内分泌]