Genetic Associations of Plasminogen Activator Inhibitor-1-Related miRNA Variants with Coronary Artery Disease

Coronary artery disease (CAD) is one of the most common types of cardiovascular disease and can lead to a heart attack as plaque gradually builds up inside the coronary arteries, blocking blood flow. Previous studies have shown that polymorphisms in the <i>PAI-1</i> gene are associated with CAD; however, studies of the <i>PAI-1</i> 3'-untranslated region, containing a miRNA binding site, and the miRNAs that interact with it, are insufficient. To investigate the association between miRNA polymorphisms and CAD in the Korean population based on post-transcriptional regulation, we genotyped five polymorphisms in four miRNAs targeting the 3'-untranslated region of <i>PAI-1</i> using real-time PCR and TaqMan assays. We found that the mutant genotype of <i>miR-30c</i> rs928508 A > G was strongly associated with increased CAD susceptibility. In a genotype combination analysis, the combination of the homozygous mutant genotype (GG) of <i>miR-30c</i> rs928508 with the wild-type genotype (GG) of <i>miR-143</i> rs41291957 resulted in increased risk for CAD. Also, in an allele combination analysis, the combination of the mutant allele (G) of <i>miR-30c</i> rs928508 and the wild-type allele (G) of <i>miR-143</i> rs41291957 resulted in increased risk for CAD. Furthermore, metabolic syndrome and diabetes mellitus showed synergistic effects on CAD risk when combined with <i>miR-30c</i> rs928508. These results can be applied to identify CAD prognostic biomarkers among miRNA polymorphisms and various clinical factors.