Epigenetic biomarker for preeclampsia-associated preterm birth and potential preventative medicine.

Abstract

Preterm birth (PTB) has dramatically increased within the population (i.e. >10%) and preeclampsia is a significant sub-category of PTB. Currently, there are no practical clinical parameters or biomarkers which predict preeclampsia induced PTB. The current study investigates the potential use of epigenetic (DNA methylation) alterations as a maternal preeclampsia biomarker. Non-preeclampsia term births were compared to preeclampsia PTBs to identify DNA methylation differences (i.e. potential epigenetic biomarker). Maternal buccal cell cheek swabs were used as a marker cell for systemic epigenetic alterations in the individuals, which are primarily due to environmentally induced early life or previous generations impacts, and minimally impacted or associated with the disease etiology or gestation variables. A total of 389 differential DNA methylation regions (DMRs) were identified and associated with the presence of preeclampsia. The DMRs were genome-wide and were predominantly low CpG density (<2 CpG/100 bp). In comparison with a previous PTB buccal cell epigenetic biomarker there was a 15% (60 DMR) overlap, indicating that the majority of the DMRs are unique for preeclampsia. Few previously identified preeclampsia genes have been identified, however, the DMRs had gene associations in the P13 K-Akt signaling pathway and metabolic gene family, such as phospholipid signaling pathway. Preliminary validation of the DMR use as a potential maternal biomarker used a cross-validation analysis on the samples and provided 78% accuracy. Although prospective expanded clinical trials in first trimester pregnancies and clinical comparisons are required, the current study provides the potential proof of concept a preeclampsia epigenetic biomarker may exist. The availability of a preeclampsia PTB maternal susceptibility biomarker may facilitate clinical management and allow preventative medicine approaches to identify and treat the preeclampsia condition prior to its occurrence.