Nilsson Eric E, Winchester Paul, Proctor Cathy, Beck Daniel, Skinner Michael K
Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, United States.
Department of Pediatrics, St. Franciscan Hospital, School of Medicine, Indiana University, Indianapolis, IN 46202-5201, United States.
Environ Epigenet. 2024 Nov 6;10(1):dvae022. doi: 10.1093/eep/dvae022. eCollection 2024.
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.
早产（PTB）在人群中的发生率显著增加（即>10%），而先兆子痫是PTB的一个重要亚类。目前，尚无实用的临床参数或生物标志物可预测先兆子痫所致的PTB。本研究调查了表观遗传（DNA甲基化）改变作为母体先兆子痫生物标志物的潜在用途。将足月非先兆子痫分娩与先兆子痫PTB进行比较，以确定DNA甲基化差异（即潜在的表观遗传生物标志物）。母体颊细胞颊拭子被用作个体全身表观遗传改变的标记细胞，这主要是由于环境诱导的早期生活或前代影响，且与疾病病因或妊娠变量的影响最小或无关。共鉴定出389个差异DNA甲基化区域（DMR），并与先兆子痫的存在相关。这些DMR在全基因组范围内，且主要是低CpG密度（<2 CpG/100 bp）。与先前的PTB颊细胞表观遗传生物标志物相比，有15%（60个DMR）重叠，这表明大多数DMR是先兆子痫特有的。虽然此前鉴定出的先兆子痫相关基因很少，但这些DMR与PI3K-Akt信号通路和代谢基因家族（如磷脂信号通路）中的基因有关联。将DMR用作潜在母体生物标志物的初步验证在样本上进行了交叉验证分析，准确率为78%。尽管需要在孕早期进行前瞻性扩大临床试验和临床比较，但本研究提供了先兆子痫表观遗传生物标志物可能存在的潜在概念验证。先兆子痫PTB母体易感性生物标志物的可用性可能有助于临床管理，并允许采取预防医学方法在先兆子痫发生之前识别和治疗该病症。
