Abstract
BackgroundTo support a hypothesis that there is an intrinsic interplay between coronary artery disease (CAD) and type 2 diabetes (T2D), we used RNA-seq to identify unique gene expression signatures of CAD, T2D, and coexisting conditions.MethodsAfter transcriptome sequencing, differential expression analysis was performed between each disordered state and normal control group. By comparing gene expression profiles 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 was extracted.ResultsA strong overlap of 191 genes across CAD, T2D and coexisting conditions, were mainly involved in a viral infectious cycle, anti-apoptosis, endocrine pancreas development, innate immune response, and blood coagulation. In T2D-specific PPI networks involving 64 genes, TCF7L2 (Degree = 169) was identified as a key gene in T2D development, while in CAD-specific PPI networks involving 64 genes, HIF1A (Degree = 124), SMAD1 (Degree = 112) and SKIL (Degree = 94) were identified as key genes in the CAD development. Interestingly, with the provided expression data from GSE23561, the three genes were all up-regulated in CAD, and SMAD1 and SKIL were specifically differentially expressed in CAD, while HIF1A was differentially expressed in both CAD and T2D, but with opposite trends.ConclusionsThis study provides some evidences in transcript level to uncover the association of T2D, CAD and coexisting conditions, and may provide novel drug targets and biomarkers for these diseases.
Highlights
To support a hypothesis that there is an intrinsic interplay between coronary artery disease (CAD) and type 2 diabetes (T2D), we used RNA-seq to identify unique gene expression signatures of CAD, T2D, and coexisting conditions
Analysis of transcriptome sequencing A total of 3.28 × 107, 2.88 × 107, 3.30 × 107, and 2.28 × 107 sequencing reads were generated from the CAD, T2D, T2D + CAD, and control groups
Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that 92 GO terms were significantly enriched, including G1/S transition of mitotic cell cycle (GO:0000082, P = 1.08E-05), transport(GO:0006810, P = 2.81E-05), etc
Summary
To support a hypothesis that there is an intrinsic interplay between coronary artery disease (CAD) and type 2 diabetes (T2D), we used RNA-seq to identify unique gene expression signatures of CAD, T2D, and coexisting conditions. Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and cause substantial public health and economic burden world-wide. It is assumed that there is an intrinsic interplay between T2D and CAD, in the form of shared etiology and pathophysiological mechanisms. The underlying mechanisms may involve a complex interplay between genes predisposing to insulin resistance and those independently regulating lipid metabolism, coagulation processes and biological responses of the arterial wall [6]. There has been limited success in correlating T2D with CAD in terms of pathophysiologic changes up to now [8]
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