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

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.