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子痫前期、早产和足月妊娠的胎盘甲基化差异。

Differential placental methylation in preeclampsia, preterm and term pregnancies.

机构信息

Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

出版信息

Placenta. 2020 Apr;93:56-63. doi: 10.1016/j.placenta.2020.02.009. Epub 2020 Feb 11.

DOI:10.1016/j.placenta.2020.02.009
PMID:32250740
Abstract

INTRODUCTION

Preeclampsia (PE) is one of the leading causes of maternal mortality and morbidity worldwide. Recently, the role of epigenetic modifications in preeclampsia has been a focus of research. This study was to identified genes or pathways that may be associated with PE, and discuss whether the changes in the methylation level of these genes is related to the pathogenesis of PE.

METHODS

The methylation levels of placental tissues between PE (n = 4), preterm birth (PB, n = 4) and term birth (TB, n = 4) were detected by Illumina Infinium HumanMethylation850 K BeadChip. Pyrosequencing and qRT-PCR were used to validated the methylation and expression levels of the genes with the most significant differences.

RESULTS

The global methylation levels of placenta tissues in PE and PB were both higher compared to TB. After eliminated the effect of gestational age, there were 808 gene probes differentially methylated in PE compared to PB. We found 137 genes with 130 genes hypermethylated and 7 genes hypomethylated. CMIP, BLCAP and MICA genes were with the most significant differential methylation. The expression level of CMIP and BLCAP were both negatively correlated to the methylation levels, while the expression level of MICA was not related to its methylation levels.

CONCLUSION

The methylation levels in placenta tissues were associated with gestational ages. We indicated the expression levels of the significantly methylated genes were negatively correlated with the methylation levels, further functional researches were still needed to find out whether they are associated with the onset of preeclampsia.

摘要

简介

子痫前期 (PE) 是全球孕产妇死亡和发病的主要原因之一。最近,表观遗传修饰在子痫前期中的作用一直是研究的焦点。本研究旨在确定可能与 PE 相关的基因或途径,并讨论这些基因的甲基化水平变化是否与 PE 的发病机制有关。

方法

通过 Illumina Infinium HumanMethylation850K BeadChip 检测 PE(n=4)、早产(PB,n=4)和足月产(TB,n=4)胎盘组织中的甲基化水平。采用焦磷酸测序和 qRT-PCR 验证差异甲基化和表达水平最显著的基因。

结果

PE 和 PB 胎盘组织的整体甲基化水平均高于 TB。消除胎龄的影响后,PE 与 PB 相比有 808 个基因探针差异甲基化。我们发现 137 个基因中有 130 个基因呈高甲基化,7 个基因呈低甲基化。CMIP、BLCAP 和 MICA 基因的差异甲基化最显著。CMIP 和 BLCAP 的表达水平与甲基化水平均呈负相关,而 MICA 的表达水平与其甲基化水平无关。

结论

胎盘组织的甲基化水平与胎龄有关。我们表明,显著甲基化基因的表达水平与甲基化水平呈负相关,需要进一步的功能研究来确定它们是否与子痫前期的发病有关。

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