关于识别60岁以下急性心肌梗死患者潜在致病基因的研究

Identification of Potential Pathogenic Genes in Patients Under 60 Years with Acute Myocardial Infarction

目的:应用生物信息学方法对GSE34198基因表达谱进行重新分析,挖掘年龄小于60岁的急性心肌梗死(AMI)患者潜在的致病和治疗基因。方法:根据GSE34198的临床资料,将患者分为年龄小于60岁的健康对照组(n=19)和急性心肌梗死组(AMI组,n=19)。应用GEO2R鉴定差异表达基因(P<0.05和|logFC|>0)。然后对其进行基因本体(GO)和通路富集分析(KEGG)。用Cytoscape 3.6.1构建蛋白相互作用网络(protein-protein interaction,PPI),鉴定出10个核心基因。从在线孟德尔遗传数据库(OMIM)中手动筛选已知AMI易感基因和保护基因。通过检索互作基因(STRING)数据库,构建核心基因和已知AMI易感基因的PPI网络。结果:共筛选出1085个差异基因,其中上调基因570个,下调基因515个。构建蛋白互作网络后,鉴定出10个核心基因。其中,MAPK1、CKAP4、LAMC1、GRB2、DYNL1和KCTD6与已知易感基因有相互作用。结论:MAPK1是60岁以下急性心肌梗死潜在的诊断和治疗靶点,另外,CKAP4是一个潜在的诊断标志物,CRB2是一个潜在的药物治疗靶点。

Objective:The gene expression profile GSE34198 was reanalyzed by using bioinformatics method to find the potential pathogenic and therapeutic genes for acute myocardial infarction(AMI)patients younger than 60 years old. Methods:According to the clinical data of GSE34198,the patients were divided into healthy control group(control group,n=19)and acute myocardial infarction group(AMI group,n=19)younger than 60. GEO2R was used to identify differentially expressed genes(P<0.05 and |logFC |≥0). Then,Gene Ontology(GO)and pathway enrichment analysis(KEGG)were performed on the DEGs. Cytoscape version 3.6.1 was used to construct protein-protein interaction(PPI)network and 10 hub genes were identified. The known susceptibility genes and protective genes of AMI were manually screened from Online Mendelian Inheritance(OMIM)database. Using the Retrieval of Interacting Genes(STRING)database,the PPI network of hub genes and known AMI susceptibility genes were constructed. Results:A total of 1085DEGs were screened out,including 570 up-regulated genes and 515 down-regulated genes. After the construction of protein-protein interaction network,10 hub genes with high connectivity were identified. Among them,MAPK1,CKAP4,LAMC1,GRB2,DYNL1 and KCTD6 interacted with existing proteins of known susceptibility genes.Conclusion:MAPK1 is a potential diagnostic and therapeutic target for AMI below 60 years old. CKAP4 is a potential diagnostic marker,and CRB2 is a potential drug therapeutic target.