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Preeclampsia Pathway Complexity Uncovered by Expression Meta-Analysis

NEW YORK (GenomeWeb) – As many as a third of genes implicated in the pregnancy complication preeclampsia may not show consistent shifts in expression in placental tissue from women with the condition, according to results of a meta-analysis published yesterday in PLOS One.

Researchers from the University of West London and Imperial College London brought together array-based gene expression profiles for placental tissue samples from 167 women with or without preeclampsia.

With these data, the team compared pathways that jumped out of both relative gene expression and absolute gene expression analyses and looked for expression shifts associated with genes suspected of contributing to preeclampsia from past studies.

"Collectively, about 36 [percent] of genes identified from literature as highly relevant for [preeclampsia] could not be confirmed as significant or consistently expressed in [preeclampsia] placentae following a large scale microarray meta-analysis," senior author Anthony Woodman, a translational research investigator at the University of West London, and his co-authors wrote.

For their study, researchers searched for available gene expression data for normal placenta, preeclampsia placenta, and term placenta samples in the Gene Expression Omnibus and ArrayExpress Archive databases. After removing duplicate, low-quality, or otherwise unsuitable samples, they were left with array-based gene expression profiles for 167 placental samples: 68 from women with preeclampsia and 99 normal placental samples.

In the normal placenta samples, the team detected 1,076 genes with enhanced expression in its absolute gene expression analysis and another 846 genes with lower expression. The absolute gene expression approach also turned up nearly 4,400 genes with elevated expression and 5,146 down-regulated genes in preeclampsia placenta samples.

On the other hand, the researchers' relative gene expression analysis pointed to 2,197 genes with muted expression in the preeclampsia samples compared to the normal placenta samples and another 2,152 genes that were dialed up in samples from those with the condition relative to those without.

And while 79 percent of the genes with higher relative expression in the preeclampsia samples also showed enhanced absolute expression, the team noted, just over half of the genes in the relative expression set across all of the samples coincided with results of the absolute gene expression analyses.

Genes showing absolute expression shifts in preeclampsia samples tended to be involved in Wnt, TGF-beta, T-cell receptor, and other signaling pathways as well as messenger RNA surveillance- and proteolysis-related genes.

Some of the same processes turned up in genes with relative expression shifts in preeclampsia, though that analysis also uncovered expression changes for several metabolism-related pathways.

The team also identified overlapping pathways in the normal and preeclampsia samples that are up- or down-regulated to different degrees in the presence or absence of preeclampsia.

Based on these and other findings, the study's authors argued that "multiple and concurrent dysregulated pathways underpin the etiology of [preeclampsia], and no single pathway could be associated with the origins of [preeclampsia]."