Epigenome analysis of normal and preeclamptic placenta samples. Homo sapiens

Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n=14), with term PE (≥37 weeks; n=19) or with preterm PE (5% methylation difference). Functional annotation of the differentially methylated genes in preterm PE placentas revealed a 32 gene cluster in the cadherin and cell adhesion functional groups (Benjamini p<0.00001). Hypermethylation of CDH11 (p=0.0143), COL5A1 (p=0.0127) and TNF (p=0.0098) and hypomethylation of NCAM1 (p=0.0158) was associated with altered mRNA expression in preterm PE placentas. These studies demonstrate aberrant methylation, correlating with disease severity, in PE placentas. Overall design: Bisulphite converted DNA from the 45 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2