与早发型子痫前期相关的胎盘 WNT2 和 DKK1 基因的 DNA 甲基化和转录改变。

Altered DNA methylation and transcription of WNT2 and DKK1 genes in placentas associated with early-onset preeclampsia.

机构信息

Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; Henan Provincial Engineering Research Center for Prenatal Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; Henan Translational Medicine Engineering Laboratory for Maternal and Children's Health, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; International Joint Research Laboratory for US-China Prenatal Medicine of Henan, China; Department of Medical research center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.

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

出版信息

Clin Chim Acta. 2019 Mar;490:154-160. doi: 10.1016/j.cca.2018.12.026. Epub 2018 Dec 27.

DOI:10.1016/j.cca.2018.12.026

PMID:30594543

Abstract

PURPOSE

The purpose of this study was to characterize the changes in DNA methylation and transcription of WNT2 and DKK1 genes in placentas associated with early-onset preeclampsia.

METHODS

The study includes three groups: patients with early-onset preeclampsia, normotensive preterm and term births. Placental tissues were collected and pyrosequencing was performed on DKK1 and WNT2 proximal promoters. Transcriptional levels of DKK1 and WNT2 genes were determined with real-time PCR.

RESULTS

DKK1 gene methylation levels were lower in placentas associated with early-onset preeclampsia compared to those associated with preterm birth (P<0.05). DKK1 mRNA expression was higher in early-onset preeclampsia placentas than those in preterm placentas (P < 0.05). WNT2 mRNA expression in early-onset preeclamptic placentas was lower than that in other two groups (P < 0.05). In the preterm and early-onset preeclampsia groups, the mRNA levels for WNT2 and DKK1 were negatively correlated (P < 0.05). In all the subjects, the levels of DKK1 mRNA and methyaltion were negatively correlated (P < 0.05).

CONCLUSION

Decreased methylation of DKK1 promoter in early-onset preeclamptic placenta tissues may up-regulate the expression of DKK1. The increased expression of DKK1 and decreased expression of WNT2 may be involved in the pathogenesis of early-onset preeclampsia.

摘要

目的

本研究旨在描述与早发型子痫前期相关的胎盘组织中 WNT2 和 DKK1 基因的 DNA 甲基化和转录变化。

方法

该研究包括三组：早发型子痫前期患者、血压正常的早产和足月分娩。收集胎盘组织，对 DKK1 和 WNT2 近端启动子进行焦磷酸测序。采用实时 PCR 法测定 DKK1 和 WNT2 基因的转录水平。

结果

与早产胎盘相比，早发型子痫前期胎盘的 DKK1 基因甲基化水平较低（P<0.05）。早发型子痫前期胎盘的 DKK1mRNA 表达高于早产胎盘（P<0.05）。早发型子痫前期胎盘的 WNT2mRNA 表达低于其他两组（P<0.05）。在早产和早发型子痫前期组中，WNT2 和 DKK1 的 mRNA 水平呈负相关（P<0.05）。在所有受试者中，DKK1mRNA 水平与甲基化呈负相关（P<0.05）。