Bioinformatics-based Approach To Study Differential Genes In Acute Myocardial Infarction And Inflammatory Bowel Disease

Research BackgroundAcute myocardial infarction（AMI）is one of the common diseases that threaten human survival and health.It is an intracoronary ischemia caused by acute thrombosis due to unstable plaque rupture or erosion,and is usually considered to be associated with various factors such as hypertension,hyperlipidemia,abnormal glucose tolerance,smoking,and obesity.An increasing number of studies are now showing a close association between acute myocardial infarction and inflammation in the body.Inflammatory bowel diseases（IBD）is an immune-mediated chronic nonspecific inflammatory disease of the intestine,mainly including ulcerative colitis（UC）and crohn’s disease（CD）,UC is characterized by continuous,The main clinical manifestations are recurrent diarrhea,mucopurulent stools and abdominal pain;CD is a chronic inflammatory granulomatous disease,which usually occurs at the end of the ileum and adjacent colon,often with abdominal pain,diarrhea,weight loss,intestinal obstruction and other manifestations.In recent years,the incidence of IBD has shown a gradually increasing trend,and its high recurrence rate has caused a huge physical,psychological and economic burden to patients.Studies have shown that the incidence of cardiovascular disease is also gradually increasing in patients with IBD,but there are fewer combined studies on acute myocardial infarction and inflammatory bowel disease at home and abroad.With the development of microarray technology and high-throughput sequencing technology,a large amount of genetic data has been generated,and it has become a current research trend to study the relationship between genes and related diseases so as to gain a deeper understanding of the diseases.The relationship between IBD and myocardial infarction is still unclear,and in this paper,a bioinformatics approach was used to investigate the relationship with a view to further exploring the association between the two.ObjectiveThe GEO（Gene Expression Omnibus）database was searched for datasets related to acute myocardial infarction and inflammatory bowel disease,and each dataset was analyzed for differential expressed genes（DEGs）,and functional and pathway enrichment analysis of differential genes was performed to clarify which significant biological activities have an impact on acute myocardial infarction and inflammatory bowel disease,and to further analyze the correlation between them.MethodBased on the GEO database under NCBI,the acute myocardial infarction dataset was obtained as GSE48060 and the inflammatory bowel disease dataset was obtained as GSE36807.Both were GPL570platform（[HG-U133＿Plus＿2]Affymetrix Human Genome U133 Plus 2.0 Array）data,GSE48060 contained transcriptomic data from 31 patients with acute myocardial infarction and 21 healthy controls,and the transcriptome data were analyzed using GEO2R,followed by the screening criteria of|log₂ FC|≥0.5 and P value≤0.05 to screen out the differential genes between the acute myocardial infarction group and the healthy control group;GSE36807 contained the transcriptome data of 13 Crohn’s disease patients and 15 ulcerative colitis patients and 7 healthy controls,and the The Crohn’s disease group data were compared with healthy controls using GEO2R analysis,after which the screening criteria of|log₂ FC|≥0.5 and P value≤0.05 were used to screen out the Crohn’s disease group and healthy controls differential genes;in the comparison of ulcerative colitis with healthy controls,the screening criteria were adjusted to|log₂ FC|≥1 and P value≤0.05in order to screen out the genes with more significant differences.GO（Gene ontology）and KEGG（Kyoto Encyclopedia of Gene And Genomes）enrichment analyses of differential genes were performed using the DAVID website.Protein-protein interaction was analyzed by using STRING website,and PPI interaction files were obtained and imported into Cytoscape to further screen key genes with significant regulatory effects.The intersection of all DEGs for acute myocardial infarction,ulcerative colitis,and Crohn’s disease by Venn diagram clarified which genes have an effect on all three at the same time,and further enrichment analysis clarified the biological activities significantly involved.ResultsIn the acute myocardial infarction group compared with the healthy control group,120 differential genes were obtained,of which 38 were up-regulated and 82 were down-regulated.Enrichment analysis by the DAVID website showed that they mainly functioned in immune response,inflammatory response,positive regulation of cell proliferation,carbohydrate binding and heparin binding,etc.Protein interaction analysis was performed using the STRING website,and further screening of key genes using Cytoscape software yielded the top 15 key genes with a high degree of interaction,such as PRF1,KLRD1 and TBX21.867 differential genes were obtained in ulcerative colitis compared with healthy controls,including 510 up-regulated genes and 357 down-regulated genes.Enrichment analysis by the DAVID website showed that they mainly play a role in signal transduction,inflammatory response,immune response and calcium binding,and15 key genes such as STAT1,IFIT3 and ISG15 were also obtained by screening using the STRING website and Cytoscape software.Comparing the Crohn’s disease group with the healthy control group,953differential genes were obtained,including 389 up-regulated genes and 564 down-regulated genes,which mainly play roles in signal transduction,cell adhesion and redox processes,and 15 key genes such as STAT1,PSMB8 and RSAD2 were obtained by the same method as above.A total of 11 differential genes were mapped by Venn diagram for the three groups,namely AQP9,PTGDR,PDGFD,PTCH1,F2R,THBS1,ACSL1,GZMB,SYTL2,CXCL5,GBP5;functional and pathway enrichment analysis was performed using the DAVID website,with P value<0.05 as the screening criterion,enriching for 10 biologic processes,1 molecular function,2 cellular components of GO functional entries,along with 1 KEGG pathway.The enrichment was mainly in processes such as inflammatory response and positive regulation of cell proliferation.Conclusion1.PRF1,KLRD1,TBX21,GZMB,KLRB1,GZMA,IL2RB,MMP9,NKG7,KLRF1,GNLY,FASLG,S 100A12,ARG1,FGFBP2 play a key role in the occurrence and development of acute myocardial infarction.2.STAT1,IFIT3,ISG15,LYN,OAS2,XAF1,IL1B,CD44,GBP2,IRF1,MX2,CXCL10,IFITM1,MMP9,MMP2 play a key role in the development of ulcerative colitis.STAT1,PSMB8,RSAD2,LYN,IRF1,JUN,GBP2,MX1,ISG15,BST2,HLA-F,XAF1,ISG20,IFI27,IFITM1 play an important role in the occurrence and development of Crohn’s disease.3.AQP9,PTGDR,PDGFD,PTCH1,F2R,THBS1,ACSL1,SYTL2,GZMB,CXCL5,and GBP5 are simultaneously associated with acute myocardial infarction,ulcerative colitis,and Crohn’s disease,of which the co-regulatory genes AQP9 and GZMB are the key regulatory genes.