Department of Obstetrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, P.R. China.
Int J Mol Med. 2012 Jul;30(1):133-41. doi: 10.3892/ijmm.2012.983. Epub 2012 Apr 25.
The development of preeclampsia (PE) seriously affects the health of the mother and the child, but the precise pathogenesis of PE remains elusive. The placenta is considered to play a key role and DNA methylation may be associated with altered placental development and function. The aim of this study was to perform a genome-wide analysis of the DNA methylation profile in placentas from pregnancies with severe preeclampsia. The authors analyzed normal and placental tissues with PE for aberrant DNA methylation using methylated DNA immunoprecipitation (MeDIP) and a human CpG island plus promoter microarray. The methylation status of identified candidate genes were validated by bisulfite sequencing PCR (BSP). Microarray analysis identified 296 genes that showed significantly aberrant DNA methylation in preeclampsia (PE). These genes were located more frequently in chromosome 1 (10.5%, P=0.005), chromosome 12 (8.1%, P=0.062) and chromosome 19 (7.4%, P=0.117). Functional analysis divided these genes into different functional networks. In addition, the methylation profile of six of these genes (CAPN2, EPHX2, ADORA2B, SOX7, CXCL1 and CDX1) in nine patients with PE was validated by BSP. This study demonstrated aberrant patterns of DNA methylation in PE, which may be involved in the pathophysiology of PE. Future work will assess the potential prognostic and therapeutic value for these findings in PE.
子痫前期 (PE) 的发展严重影响母婴健康，但 PE 的精确发病机制仍难以捉摸。胎盘被认为起着关键作用，而 DNA 甲基化可能与胎盘发育和功能的改变有关。本研究旨在对严重子痫前期胎盘的 DNA 甲基化谱进行全基因组分析。作者使用甲基化 DNA 免疫沉淀 (MeDIP) 和人类 CpG 岛加启动子微阵列分析了正常和有 PE 的胎盘组织中的异常 DNA 甲基化。通过亚硫酸氢盐测序 PCR (BSP) 验证了鉴定候选基因的甲基化状态。微阵列分析确定了 296 个在子痫前期 (PE) 中表现出明显异常 DNA 甲基化的基因。这些基因更多地位于染色体 1 (10.5%，P=0.005)、染色体 12 (8.1%，P=0.062) 和染色体 19 (7.4%，P=0.117)。功能分析将这些基因分为不同的功能网络。此外，通过 BSP 验证了 9 名 PE 患者中其中 6 个基因 (CAPN2、EPHX2、ADORA2B、SOX7、CXCL1 和 CDX1) 的甲基化谱。本研究表明 PE 中存在异常的 DNA 甲基化模式，这可能与 PE 的病理生理学有关。未来的工作将评估这些发现在 PE 中的潜在预后和治疗价值。
