Department of General Medicine, The Affiliated Hospital, Qingdao University, Qingdao, China.
Institute for Translational Medicine, Qingdao University, Qingdao, China.
J Cell Mol Med. 2018 Nov;22(11):5418-5428. doi: 10.1111/jcmm.13813. Epub 2018 Aug 13.
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.
微小 RNA（miRNA）是一种非编码 RNA，作为心脏发育和心血管疾病的转录后调控因子发挥作用。miRNA 基因中的单核苷酸多态性（SNP）是人类基因组中一种新的遗传变异类型，可增加心血管疾病的风险。在这里，我们鉴定出 miR-499 前体（pre-miR-499）中的一个 A→G（rs3746444）多态性，该多态性影响 miR-499-5p 的成熟，并通过在 pre-miR-499 二级结构中稳定的 A-U 碱基对转换为摆动的 G-U 碱基对，改变其抗凋亡功能。此外，我们的结果表明，与对照组相比，血浆 miR-499-5p 的浓度可与心肌梗死（MI）和心力衰竭（HF）患者相关，并且 miR-499 中的 rs3746444 多态性可影响其在血浆中的丰度。最后，我们的结果还表明，miR-499 多态性的变异显著影响心肌梗死的严重程度。这是首次报道该多态性对 miR-499-5p 成熟及其在 MI 中抗凋亡作用的生物学意义。这些发现可能为基于 miRNA SNPs 更好地理解心脏病中的个体变异性铺平道路，并有助于在个性化水平上更好地治疗疾病严重程度。
