Role of Genetic & Epigenetic Modifications of Low-Density Lipoprotein Receptor (LDLR) Gene in South Indian Acute Myocardial Infraction Patients

Abstract

Background: Acute Myocardial Infarction (AMI) has conventional risk factors as well as genetic and epigenetic modifications of various genes. Among them gene coding for Low density lipoprotein receptor (LDLR) plays a strategic role in cholesterol homeostasis by eliminating excess LDL-C in blood. LDLR gene promoter polymorphism & DNA methylation status might regulate the expression of genes & its activity. Objective: The present study is designed to evaluate the association of LDLR gene promoter c.-139delCTCCCCCTGC polymorphism & DNA methylation status with Acute Myocardial Infarction (AMI). Methods: 300 angiographically documented MI patients and 300 healthy individuals were recruited for the study. Genomic DNA & RNA was extracted from the whole blood using commercially available assay kits further RNA was converted to cDNA. Biochemical parameters like Total cholesterol, LDL-C, HDL-C, and Triglycerides were estimated using kit methods. Results: The risk factors like systolic, diastolic blood pressures, hypertension, diabetes mellitus, smoking, lipids were found to be significantly higher in AMI patients compared to controls. The genotype and allele distributions of the LDLR c.-139del polymorphism revealed that DD genotype & D-allele were found to be higher among the AMI patients than that of controls. Furthermore, we have observed LDLR gene differential promoter DNA methylation status & mRNA expression. In addition, Insilco analysis have shown that there is a change in TF binding at the Insertion & Deletion sites. Conclusion: The findings of the study suggest that the LDLR c.-139del DD genotype might be used as prognostic marker in risk prediction of Acute Myocardial Infarction.