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.
