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eNOS-G894T 基因多态性与子痫前期风险:病例对照研究、更新的荟萃分析和生物信息学分析。

The eNOS-G894T genetic polymorphism and risk of preeclampsia: A case-control study, an updated meta-analysis, and a bioinformatic assay.

机构信息

Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

出版信息

Cytokine. 2023 Sep;169:156283. doi: 10.1016/j.cyto.2023.156283. Epub 2023 Jun 23.

Abstract

OBJECTIVES

Preeclampsia (PE) is a leading cause of maternal death worldwide and involves vascular endothelial dysfunction. The aim of this study was to investigate the association of the G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene and the risk of preeclampsia in a case-control design in an Iranian population, which was followed by a meta-analysis and an in silico approach.

METHODS

In the case-control study, 300 people including 135 pregnant women with preeclampsia and 165 healthy pregnant women were included. The genotype of G894T polymorphism was determined by the PCR-RFLP method. We searched authoritative scientific databases to find eligible studies for meta-analysis. The odds ratio with a 95% confidence interval was estimated to find the strength of the association of the mentioned polymorphism with the risk of preeclampsia. In addition, the effect of G894T transversion on eNOS gene function was evaluated by some bioinformatics tools.

RESULTS

Our case-control data showed that the G894T polymorphism is associated with an increased risk of preeclampsia. In the meta-analysis, 33 eligible studies were included, and the results showed that the G894T polymorphism is associated with an increased risk of preeclampsia in the overall analysis and some stratified analyses. In addition, the structural analysis showed that the G894T variant can affect the splicing process as well as the protein stability.

CONCLUSIONS

Based on the results, the aforementioned polymorphism may be a risk factor for preeclampsia and could be considered a potential molecular biomarker for screening susceptible individuals.

摘要

目的

子痫前期(PE)是全球范围内导致产妇死亡的主要原因,涉及血管内皮功能障碍。本研究旨在通过病例对照设计,在伊朗人群中研究内皮型一氧化氮合酶(eNOS)基因 G894T 多态性与子痫前期风险的相关性,并进行荟萃分析和计算机模拟。

方法

在病例对照研究中,共纳入 300 人,包括 135 例子痫前期孕妇和 165 例健康孕妇。采用 PCR-RFLP 法检测 G894T 多态性的基因型。我们检索权威科学数据库,以找到适合荟萃分析的研究。采用比值比(OR)及其 95%置信区间(CI)来评估该多态性与子痫前期风险之间的关联强度。此外,还使用一些生物信息学工具评估 G894T 转换对 eNOS 基因功能的影响。

结果

我们的病例对照数据表明,G894T 多态性与子痫前期的发生风险增加相关。荟萃分析纳入 33 项符合条件的研究,结果表明,总体分析和一些分层分析均显示 G894T 多态性与子痫前期的发生风险增加相关。此外,结构分析表明,G894T 变体可影响剪接过程和蛋白稳定性。

结论

基于这些结果,上述多态性可能是子痫前期的一个风险因素,可被视为筛查易感个体的潜在分子生物标志物。

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