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一个与 选择性剪接相关的 SNP 与中国人群冠心病患者氯吡格雷抵抗相关。

A SNP involved in alternative splicing of is associated with clopidogrel resistance in coronary heart disease in Chinese population.

机构信息

School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.

The Second Hospital of Lanzhou University, Lanzhou 730000, China.

出版信息

Aging (Albany NY). 2020 Nov 20;12(24):25684-25699. doi: 10.18632/aging.104177.

Abstract

Although many scientists are studying the association between genetic polymorphism of and CR in patients, the molecular mechanism has not been further studied in patients with CHD. This study investigated the relationship between SNP of the gene in patients with CHD and CR, and whether the polymorphism of the gene affects the AS of the gene. 741 patients were enrolled in the study, 316 CR cases and 425 NCR cases. The correlation between CR risk and clinical-pathological characteristics were studied. Additionally, the five SNPs were analysed by PCR and Mass Array genotyping methods. Furthermore, silicon analysis was used to predict whether the polymorphism affects the process of AS. Results showed that there was a significant correlation between rs1045642 polymorphism and CR in genotyping and allele analysis. The rs1045642 polymorphism of the gene of CHD patients carrying the A allele are more likely to develop CR. Silicon analysis showed that rs1045642 generated a new ESE sequence which might affect AS of gene. We hypothesize that the mechanism of CR might be caused by a change in the AS caused by the polymorphism of the gene. Thus, this work provides guidance for the clinical use of clopidogrel.

摘要

尽管许多科学家正在研究基因多态性与 CR 之间的关联,但在 CHD 患者中尚未进一步研究其分子机制。本研究探讨了 CHD 患者中基因 SNP 与 CR 的关系,以及基因多态性是否影响基因的 AS。研究纳入了 741 例患者,其中 316 例为 CR 病例,425 例为 NCR 病例。研究了 CR 风险与临床病理特征之间的相关性。此外,采用 PCR 和 MassArray 基因分型方法分析了 5 个 SNP。进一步通过硅分析预测多态性是否影响 AS 过程。结果表明,rs1045642 基因多态性与基因分型和等位基因分析中的 CR 显著相关。携带 A 等位基因的 CHD 患者的基因 rs1045642 多态性更易发生 CR。硅分析表明,rs1045642 产生了一个新的 ESE 序列,可能影响基因的 AS。我们假设 CR 的机制可能是由基因多态性引起的 AS 改变引起的。因此,这项工作为氯吡格雷的临床应用提供了指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac76/7803500/02f5c87c8f1d/aging-12-104177-g001.jpg

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