Genetic Variations in microRNA and their Association with Coronary Artery Disease: A Comprehensive Meta-Analysis

Abstract

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, with genetic and molecular mechanisms playing a crucial role in its development. Among these, microRNAs (miRNAs) are important post-transcriptional regulators that affect endothelial function, inflammation, and lipid metabolism. This meta-analysis aimed to assess the association between four common miRNA polymorphisms, miR-146a (rs2910164), miR-149a (rs2292832), miR-196a2 (rs11614913), and miR-499 (rs3746444) and susceptibility to CAD. Relevant studies published up to 2025 were systematically collected from PubMed, Embase, and Google Scholar following PRISMA guidelines. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under various genetic models using either random- or fixed-effects models depending on heterogeneity. A total of 13,229 CAD cases and corresponding controls were included. The results indicated that miR-146a, miR-196a2, and miR-499 polymorphisms were significantly linked to CAD risk, especially among Asian populations, while miR-149a showed no overall association. Sensitivity analyses confirmed the stability of these findings, although moderate heterogeneity was observed in some models. Publication bias was evaluated using Begg’s funnel plot and Egger’s test, showing no significant asymmetry. These findings suggest that specific miRNA variants may play a role in CAD pathogenesis by modifying gene expression related to vascular inflammation and remodeling. However, due to the observed heterogeneity and limited data in certain ethnic groups, these associations should be interpreted with caution. Further large-scale, multiethnic studies are necessary to confirm these results and better understand the underlying molecular mechanisms.

Keywords: microRNA, Coronary artery disease, Polymorphism, Genetics