The role of single nucleotide polymorphisms (SNPs) in the etiopathogenesis of cardiovascular diseases is well known. The effect of SNPs on disease predisposition has been established not only for protein coding genes but also for genes encoding microRNAs (miRNAs). The miR-143/145 cluster is smooth muscle cell-specific and implicated in the pathogenesis of atherosclerosis. Whether SNPs within the genomic sequence of the miR-143/145 cluster are involved in cardiovascular disease development is not known. We thus searched annotated sequence databases for possible SNPs associated with miR-143/145. We identified one SNP, rs41291957 (G > A), located −91 bp from the mature miR-143 sequence, as the nearest genetic variation to this miRNA cluster, with a minor allele frequency > 10%. In silico and in vitro approaches determined that rs41291957 (A) upregulates miR-143 and miR-145, modulating phenotypic switching of vascular smooth cells towards a differentiated/contractile phenotype. Finally, we analysed association between rs41291957 and CAD in two cohorts of patients, finding that the SNP was a protective factor. In conclusion, our study links a genetic variation to a pathological outcome through involvement of miRNAs.

中文翻译：

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rs41291957 控制 miR-143 和 miR-145 表达并影响冠状动脉疾病风险

单核苷酸多态性（SNP）在心血管疾病发病机制中的作用是众所周知的。SNP 对疾病易感性的影响不仅针对蛋白质编码基因，而且针对编码 microRNA (miRNA) 的基因。miR-143/145 簇是平滑肌细胞特异性的，与动脉粥样硬化的发病机制有关。miR-143/145 簇基因组序列内的 SNP 是否参与心血管疾病的发展尚不清楚。因此，我们在带注释的序列数据库中搜索了与 miR-143/145 相关的可能的 SNP。我们鉴定了一个 SNP，rs41291957 (G > A)，位于成熟 miR-143 序列的 -91 bp 处，是最接近该 miRNA 簇的遗传变异，其次要等位基因频率 > 10%。计算机和体外方法确定rs41291957 (A) 上调 miR-143 和 miR-145，调节血管平滑细胞向分化/收缩表型的表型转换。最后，我们分析了两组患者中rs41291957与 CAD 之间的关联，发现 SNP 是一个保护因素。总之，我们的研究通过 miRNA 的参与将遗传变异与病理结果联系起来。