Gene linkage and genomic characteristic analysis between type 2 diabetes mellitus and coronary heart disease

Abstract

Introduction: coronary artery disease (CAD) is one of the most common complications in type 2 diabetes mellitus (T2DM). Although the mechanism is still unclear, T2DM may contribute through several pathways leading to atherogenic plaque of CAD. Genetic factor plays a key role to the development T2DM-associated CAD. Objectives: This study aimed to (1) determine overlapping genes between T2DM and CAD and analyze the characteristics of the overlapping genes and (2) show network of overlapping genes. Materials and Methods: We used two datasets from two different databases. First dataset was taken from CADgene database (http://www.bioguo.org/CADgene/) and the second was T2DGADB database (http://t2db.khu.ac.kr:8080/index.jsp). We did gene enrichment analysis by using GOrilla (biological processes, molecular functions and cellular components) and DAVID (gene functional classification). We also analyzed protein-protein interaction (PPI) by using STRING. Results: 131 overlapping genes was generated from T2DGADB (530) and CADgene (604). Gene functional classification resulted 5 different groups, consisting of genes acting in lipoprotein metabolism (LIPC, LPL, CETP, APOA2, APOA5, APOC3, APOB, APOA1) ES 9.98, PPARs (PPARA, PPARD, PPARG, VDR) ES 6.88, cytokines (IFNG, IL4, IL6, TNF, IL1B, IL10) ES 6.71, chemokines (CX3CR1, ADRA2B, CCR5, CXCR4) ES 4.67, and KLFs (KLF2, KLF14, FOXO1, KLF5) ES 3.01. GOrilla resulted that biological process and molecular function analyses presented genes mainly involved in lipoprotein, cholesterol, and G protein coupled receptor regulation, whereas cellular component analysis resulted the involvement of the genes related with very-low-density lipoprotein and chylomicron. Moreover, STRING result showed that overlapping genes resulted a network composed by 4 main subnetworks. The first was formed by nodes, including LIPC, CETP, MTTP, LPL, LDLR, APOC3, APOB, APOE, APOA1, APOA3, and APOA5. The second subnetwork was composed of PPARG, PPARA, PPARD, PPARGC1A genes, while the third subnetwork was formed by three main genes, IRS1, IRS2 and IGF1. The last subnetwork was formed by CXCL5, CCR5, ADRA2B, NPY, AGT, CXCR4, CCL2, and CX3CR1. Conclusion: we found that overlapping genes were classified in 5 different groups, consisting of genes acting in lipoprotein metabolism, PPARs, cytokines, chemokines, and KLFs. the other enrichment analysis presented that the genes were mainly involved in lipoprotein, cholesterol, G protein coupled receptor regulation, and very-low-density lipoprotein and chylomicron involvement. Furthermore, the overlapping genes compiled to four subnetworks, which were lipoprotein, PPAR, insulin signaling, and inflammation subnetwork. PPAR subnetwork likely showed as an interconnection between lipoprotein and insulin signaling subnetwork.