Sarı-Tunel Fatma, Demirkan Ayse, Vural Burcak, Yıldız Cenk Eray, Komurcu-Bayrak Evrim
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Istanbul, Turkey.
Graduate School Institute of Health Sciences, Istanbul University, 34093 Istanbul, Turkey.
Genes (Basel). 2024 Dec 31;16(1):40. doi: 10.3390/genes16010040.
Chronic venous insufficiency (CVI), a chronic vascular dysfunction, is a common health problem that causes serious complications such as painful varicose veins and even skin ulcers. Identifying the underlying genetic and epigenetic factors is important for improving the quality of life of individuals with CVI. In the literature, many genes, variants, and miRNAs associated with CVI have been identified through genomic and transcriptomic studies. Despite molecular pathogenesis studies, how the genes associated with CVI are regulated by miRNAs and the effect of variants in binding regions on expression levels are still not fully understood. In this study, previously identified genes, variants, and miRNAs associated with CVI, common variants in the mRNA-miRNA binding regions, were investigated using in silico analyses. For this purpose, miRNA research tools, MBS (miRNA binding site) database, genome browsers, and the eQTL Calculator in the GTEx portal were used. We identified SNVs associated with CVI that may play a direct role in the miRNA-mediated regulation of the , , , , , , , , , and genes. In addition, when the common SNVs in the mRNA binding region of 75 unique CVI related-miRNAs in five candidate genes associated with CVI were examined, seven miRNAs associated with the expression profiles of , , and genes were identified. In conclusion, the relationship between genetic markers identified in the literature that play a role in the pathogenesis of the CVI and the expression profiles was evaluated for the first time in the mRNA-miRNA interaction axis.
慢性静脉功能不全（CVI）是一种慢性血管功能障碍，是一个常见的健康问题，会导致诸如疼痛性静脉曲张甚至皮肤溃疡等严重并发症。识别潜在的遗传和表观遗传因素对于提高CVI患者的生活质量很重要。在文献中，通过基因组和转录组研究已经鉴定出许多与CVI相关的基因、变体和微小RNA（miRNA）。尽管进行了分子发病机制研究，但与CVI相关的基因如何受miRNA调控以及结合区域中的变体对表达水平的影响仍未完全了解。在本研究中，使用计算机分析研究了先前鉴定的与CVI相关的基因、变体和miRNA，即mRNA-miRNA结合区域中的常见变体。为此，使用了miRNA研究工具、MBS（miRNA结合位点）数据库、基因组浏览器以及GTEx门户中的eQTL计算器。我们鉴定出了与CVI相关的单核苷酸变异（SNV），它们可能在miRNA介导的[具体基因1]、[具体基因2]、[具体基因3]、[具体基因4]、[具体基因5]、[具体基因6]、[具体基因7]、[具体基因8]、[具体基因9]和[具体基因10]基因调控中起直接作用。此外，当检查与CVI相关的五个候选基因中75个独特的CVI相关miRNA的mRNA结合区域中的常见SNV时，鉴定出了七个与[具体基因11]、[具体基因12]和[具体基因13]基因表达谱相关的miRNA。总之，首次在mRNA-miRNA相互作用轴上评估了文献中鉴定的在CVI发病机制中起作用的遗传标记与表达谱之间的关系。
