Investigating Coronary Artery Disease methylome through targeted bisulfite sequencing

Abstract

AbstractBackgroundGene environment interactions leading to epigenetic alterations play pivotal role in the pathogenesis of Coronary Artery Disease (CAD). Altered DNA methylation is one such epigenetic factor that could lead to altered disease etiology. In this study, we comprehensively identified methylation sites in several genes that have been previously associated with young CAD patients.MethodsThe study population consisted of 42 healthy controls and 33 young CAD patients (age group < 50 years). We performed targeted bisulfite sequencing of promoter as well as genic regions of several genes in various pathways like cholesterol synthesis and metabolism, endothelial dysfunction, apoptosis, which are implicated in the development of CAD.ResultsWe observed that the genes likeGALNT2, HMGCRwere hypermethylated in the promoter whereasLDLRgene promoter was hypomethylated indicating that intracellular LDL uptake was higher in CAD patients. AlthoughAPOA1did not show significant change in methylation butAPOC3andAPOA5showed variation in methylation in promoter and exonic regions. Glucokinase (GCK) and endothelial nitric oxide synthase 3(NOS3)were hyper methylated in the promoter. Genes involved in apoptosis(BAX/BCL2/AKT2)and inflammation (PHACTR1/LCK) also showed differential methylation between controls and CAD patients.ConclusionsThis study is unique because it highlights important gene methylation alterations which might predict the risk of young CAD in Indian population. Large scale studies in different populations would be important for validating our findings and understanding the epigenetic events associated with CAD.