Genetic and epigenetic factors regulating the expression and function of the vitamin D receptor in patients with coronary artery disease

Abstract

Coronary artery disease (CAD) remains the leading cause of death and disability in developed countries. Using traditional risk factors for CAD, it is possible to predict the likelihood of acute coronary events in no more than 50% of cases. Therefore, the study of influence of genetic and epigenetic factors on the development of CAD is extremely important. Research in recent years has shown that vitamin D deficiency is a new risk factor for atherosclerosis and immune inflammation. Vitamin D implements protective effects against immune inflammation through receptors in the vascular wall. A single nucleotide polymorphism of the vitamin D receptor (VDR) gene is a potential risk factor for CAD associated with low vitamin D levels. VDR expression correlates with the expression of pro-inflammatory cytokines and is regulated by microRNAs — microRNA-125a-5p, microRNA-125b-5p, microRNA-214-3p and microRNA-21 These microRNAs regulate the action, synthesis and metabolism of vitamin D and can themselves be influenced by VDR signals through dynamic feedback, which can lead to destabilization of mRNA and inhibition of translation. This literature review highlights the effect of a single nucleotide polymorphism of the VDR gene and microRNA on the pathogenetic mechanisms of CAD.

The Role of Polymorphism in the Endothelial Homeostasis and Vitamin D Metabolism Genes in the Severity of Coronary Artery Disease

“…Scientists have discovered more than 470 SNPs in the VDR gene, and thoroughly studied the role of four SNPs, rs2225870, rs1544410, rs7975232 and rs731236, in the pathogenesis of different diseases (cancer, diabetes, Parkinson’s disease, myocardial infarction and CAD) [ 52 , 53 , 54 , 55 ]. Studies have shown that genetic polymorphism in the VDR gene is associated with CAD risk in different populations.…”

Genomic or Non-Genomic? A Question about the Pleiotropic Roles of Vitamin D in Inflammatory-Based Diseases

“…VDR expression is differently correlated with inflammatory cytokines expression and miRNAs regulation, mainly miRNA-21, -214, and -125. A single nucleotide polymorphism of the VDR gene constitutes a risk factor for coronary artery disease [ 86 ]. In macrophages, which are essential immune cells during the vascular inflammatory response, upregulation of miRNA-155 is associated with LPS induced hyper-inflammatory process by the inhibition of suppressor of cytokine signaling 1 (SOCS1).…”