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纤溶酶原激活物抑制剂-1 相关 miRNA 变异与冠状动脉疾病的遗传关联。

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

机构信息

Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea.

CHA Bundang Medical Center, Department of Cardiology, CHA University, Seongnam 13496, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Oct 27;25(21):11528. doi: 10.3390/ijms252111528.

DOI:10.3390/ijms252111528
PMID:39519081
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11546797/
Abstract

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 gene are associated with CAD; however, studies of the 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 using real-time PCR and TaqMan assays. We found that the mutant genotype of rs928508 A > G was strongly associated with increased CAD susceptibility. In a genotype combination analysis, the combination of the homozygous mutant genotype (GG) of rs928508 with the wild-type genotype (GG) of rs41291957 resulted in increased risk for CAD. Also, in an allele combination analysis, the combination of the mutant allele (G) of rs928508 and the wild-type allele (G) of rs41291957 resulted in increased risk for CAD. Furthermore, metabolic syndrome and diabetes mellitus showed synergistic effects on CAD risk when combined with rs928508. These results can be applied to identify CAD prognostic biomarkers among miRNA polymorphisms and various clinical factors.

摘要

冠状动脉疾病 (CAD) 是最常见的心血管疾病类型之一,由于斑块在冠状动脉内逐渐积聚,导致血流阻塞,可引发心脏病发作。先前的研究表明,基因中的多态性与 CAD 相关;然而,针对包含 miRNA 结合位点的 3'-非翻译区以及与其相互作用的 miRNAs 的研究还不够充分。为了基于转录后调控研究 miRNA 多态性与韩国人群 CAD 的关联,我们使用实时 PCR 和 TaqMan 检测法针对四个靶向的 miRNA 的 3'-非翻译区中的五个多态性进行了基因分型。我们发现,rs928508 的突变基因型 A > G 与 CAD 易感性增加强烈相关。在基因型组合分析中,rs928508 的纯合突变基因型 (GG) 与 rs41291957 的野生型基因型 (GG) 的组合导致 CAD 风险增加。此外,在等位基因组合分析中,rs928508 的突变等位基因 (G) 与 rs41291957 的野生型等位基因 (G) 的组合导致 CAD 风险增加。此外,代谢综合征和糖尿病与 rs928508 联合时对 CAD 风险具有协同作用。这些结果可应用于鉴定 miRNA 多态性和各种临床因素中的 CAD 预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdcb/11546797/8f2fb0f8687b/ijms-25-11528-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdcb/11546797/8f2fb0f8687b/ijms-25-11528-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdcb/11546797/8f2fb0f8687b/ijms-25-11528-g001.jpg

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本文引用的文献

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rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk.rs41291957 控制 miR-143 和 miR-145 的表达,并影响冠心病的风险。
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