262: Molecular signatures of preeclampsia in human term placentas


      To generate genome-wide gene expression profiles of human placentas from normal, growth-restricted, and preeclamptic term pregnancies; to identify molecular signatures of these conditions.

      Study Design

      Eighty-nine human placentas from normal (43), growth-restricted (27), and preeclamptic (19) term pregnancies were profiled using Illumina Human-6 Beadarrays interrogating a total of 48,701 probes across the human genome.


      At a conservative statistical threshold (Bonferonni corrected p < 0.05), we identified a set of 90 differentially expressed genes between control and preeclamptic placentas as candidates for a molecular signature of the fetal contribution to this condition. Functional analysis of this molecular signature found significant enrichment for proteins associated with the cell membrane, signal transduction (in particular the Ras Homology A, RhoA associated signaling pathway), and nucleotide excision repair (a potential mechanism for active DNA demethylation). Significant enrichment was also observed for differentially expressed genes in sickle cell patients suggesting an overlapping molecular basis for these different vascular disorders.


      The molecular signature identified here may serve as the basis for understanding the underlying etiology of this disorder, as well as developing the tools for early-term clinical diagnosis and intervention. DNA methylation states are known to affect gene expression; active DNA demethylation has been proposed to occur via a base excision repair pathway, although a specific DNA demethylase has yet to be identified. The observed enrichment of proteins in the nucleotide excision repair pathway suggests that perturbations in the epigenetic state may contribute to the onset of preeclampsia.