A polymorphism rs3746444 within the pre-miR-499 alters the maturation of miR-499-5p and its antiapoptotic function.

microRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional regulators of cardiac development and cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in miRNA genes are a novel class of genetic variations in the human genome that confer the risk of cardiovascular diseases. Here, we identified a polymorphism A→G (rs3746444) in miR-499 precursor (pre-miR-499) that affects the maturation of miR-499-5p and alters its antiapoptotic function by converting stable A-U base pair to wobble G-U base pair in pre-miR-499 secondary structure. Furthermore, our results showed that the concentrations of plasma miR-499-5p could be correlated with myocardial infarction (MI) and heart failure (HF) patients in comparison with control subjects and polymorphism rs3746444 in miR-499 could influence its abundance in plasma. Finally, our results also showed that the variant of polymorphism in miR-499 influenced the severity of the myocardial infarction significantly. This is the first report to highlight the biological significance of this polymorphism on the maturation of miR-499-5p and its antiapoptotic role during MI. These findings may pave a way to better understand the individual variability based on miRNA SNPs in heart diseases and may contribute to better treatment for disease severity on a personalized level.