糖尿病、冠状动脉疾病及两病并存患者基因表达差异分析  

The differences of gene expression in type 2 diabetes and coronary artery disease

作　　者：宫蕊 热依拉·牙合甫[2] 张国亮[3] 任珊[4] 陈曼丽[3] 陈孟晖[3] 李海滨[5] 赵成 GONG Rui;REYILA·Yahefu;ZHANG Guoliang(Hebei Provincial Children’s Hospital, Hebei, Shijiazhuang 050031,China)

机构地区：[1]河北省儿童医院,石家庄市050031 [2]新疆医科大学第二附属医院 [3]河北省石家庄市第三医院 [4]河北省人民医院 [5]河北医科大学第三医院,050051 [6]河北省石家庄市长安区谈固东区社区卫生服务站

出　　处：《河北医药》2020年第10期1449-1455,共7页Hebei Medical Journal

摘　　要：目的研究分析2型糖尿病(T2DM)、冠状动脉疾病(CAD)病理共有的关键调控基因及分子机制,并进一步分析上述2种疾病之间是否存在共有的调控基因,以期早诊断早干预。方法对确诊2型糖尿病、冠状动脉疾病、同患两病患者及正常对照组的外周血单核细胞进行转录组测序(RNA-sequencing)。利用基因本体论数据库(gene ontology,GO)进行功能富集分析;京都基因和基因组百科全书数据库(KEGG)进行通路富集分析。然后应用生物通用交互数据集库(BioGRID,http://thebiogrid.org/)分析获得与冠状动脉疾病和(或)2型糖尿病的差异表达基因产物互作的蛋白质,并构建蛋白质-蛋白质互作关系网络,构建可视化网络。最后对基因表达数据库(GEO)中与2型糖尿病和冠状动脉疾病相关数据集,验证冠状动脉疾病和(或)2型糖尿病中的候选差异表达基因的表达水平。结果共计191个基因在2型糖尿病、冠状动脉疾病和两病共存条件下均差异表达;2型糖尿病特异性的蛋白质-蛋白质互作关系网络中,TCF4(Degree=169)、SKP1(Degree=164)、UBE2W(Degree=75)为枢纽蛋白;冠状动脉疾病特异性的蛋白质-蛋白质互作关系网络中,HIF1A(Degree=124)、SMAD1(Degree=112)和SKIL(Degree=94)为枢纽蛋白;通过GSE23561基因表达数据集对候选差异表达基因验证,其中HIF1A、SMAD1和SKIL三个基因在冠状动脉疾病中的表达水平均显著高于正常对照,HIF1A在2型糖尿病中显著下调。结论共同差异表达基因主要参与病毒感染周期、抗凋亡、胰腺发育、先天免疫应答和凝血功能等生物功能和代谢通路。TCF4、SKP1与UBE2W为2型糖尿病的关键调控基因;HIF1A、SMAD1与SKIL为冠状动脉疾病的关键调控基因。冠状动脉疾病、2型糖尿病、2型糖尿病+冠状动脉疾病之间存在共有的调控基因,可能因其具有相似病理分子机制。Objective To investigate the critical controlling gene and molecule mechanism in coronary artery disease(CAD)and type 2 diabetes(T2D),and to analyze further whether there exists common controlling gene in the two diseases for early diagnosis and early treatment.Methods After transcriptome sequencing,differential expression analysis was performed between each disordered state and normal control group.By comparing gene expression levels of CAD,T2D,and coexisting conditions,common and specific patterns of each disordered state were displayed.To verify the specific gene expression patterns of CAD or T2D,the gene expression data of GSE23561 were extracted.Results A total of 191 genes showed differential expression in T2D,CAD and coexisting conditions,which were mainly involved in a viral infectious cycle,anti-apoptosis,endocrine pancreas development,innate immune response,and blood coagulation.In T2D-specific PPI networks involved 64 genes,and TCF4(Degree=169),SKP1(Degree=164)and UBE2W(Degree=75)were key protein,and in CAD-specific PPI networks involving 64 genes,HIF1A(Degree=124),SMAD1(Degree=112)and SKIL(Degree=94)were identified as key protein,in which,the expression levels of HIF1A,SMAD1 and SKIL genes in CAD were high than those in control group,however,the expression levels of HIF1A in T2D were significantly decreased.Conclusion The common differential expression genes are mainly involved in viral infectious cycle,anti-apoptosis,pancreas development,innate immune response,and blood coagulation.TCF4,SKP1 and UBE2W are key controlling gene in T2D,and HIF1A,SMAD1 and SKIL are key controlling genein CAD,There exists common controlling gene in CAD,T2D and CAD+T2D,which may have similar pathological molecule mechanism.

关 键 词：冠状动脉疾病 2型糖尿病 转录组测序 差异表达基因 

分 类 号：R587.1[医药卫生—内分泌] R543.3[医药卫生—内科学]