Evaluation of link between Diabetes and Cardiovascular Diseases through Gene Set Enrichment analysis

Abstract

Diabetes is metabolic disorder that is characterized by hyperglycemia, resulting from defects of insulin secretions. Chronic diabetic conditions are associated with long term damage and dysfunctioning of certain organs especially eyes, kidneys, nerves, heart and blood vessels. Cardiovascular diseases is a group of heart diseases caused by increased heart strain leading to heart attack or heart failure. Type II diabetes lies among major risk factor of disruption in cardiovascular events. There is a need to explore diseases at genomic level to find out certain biomarkers and DEGs that can indicate the risk of heart disease in a diabetic individual. Main objective of this study is to find out differentially expressed genes and potential targets common among type II diabetes and cardiovascular diseases followed by identification of possibly affected regulatory pathways. Objectives are achieved using microarray and NGS technique to get significant DEGs. Common DEGs among both phenotypes are obtained through comparative analysis of microarray and RNA-seq results followed by performing gene set enrichment analysis to get most enriched pathway. Pathway is modeled in Simbiology for simulation and sensitivity analysis using quantitative modeling approach. From results of overall analysis it can be concluded that dysregulation of FOXO1 can inhibit the DNA activity. Akt, FOXO1, CaMKII and P13K are the most important targets involved in leading a diabetic patient more towards risk of having cardiovascular disease ending up as heart failure. Activation of P13K is alarming in diabetic patients as it is the sign of early stage cardiovascular disease also proved by previous studies. Regulation of FOXO4 was observed in GSEA that was associated with negative cell cycle proliferation and viral gene expression transcription. Activation and behavior of these entities and pathways can be monitored in diabetic patient to check the risk of having disruption in cardiovascular events. Future studies can help in validation of these targets using experimental approaches.