Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26171964
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular
Pathway Related to Preeclampsia
#MMPMID26171964
van Uitert M
; Moerland PD
; Enquobahrie DA
; Laivuori H
; van der Post JA
; Ris-Stalpers C
; Afink GB
PLoS One
2015[]; 10
(7
): e0132468
PMID26171964
show ga
Studies using the placental transcriptome to identify key molecules relevant for
preeclampsia are hampered by a relatively small sample size. In addition, they
use a variety of bioinformatics and statistical methods, making comparison of
findings challenging. To generate a more robust preeclampsia gene expression
signature, we performed a meta-analysis on the original data of 11 placenta RNA
microarray experiments, representing 139 normotensive and 116 preeclamptic
pregnancies. Microarray data were pre-processed and analyzed using standardized
bioinformatics and statistical procedures and the effect sizes were combined
using an inverse-variance random-effects model. Interactions between genes in the
resulting gene expression signature were identified by pathway analysis
(Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and
protein-protein associations (STRING). This approach has resulted in a
comprehensive list of differentially expressed genes that led to a 388-gene
meta-signature of preeclamptic placenta. Pathway analysis highlights the
involvement of the previously identified hypoxia/HIF1A pathway in the
establishment of the preeclamptic gene expression profile, while analysis of
protein interaction networks indicates CREBBP/EP300 as a novel element central to
the preeclamptic placental transcriptome. In addition, there is an apparent high
incidence of preeclampsia in women carrying a child with a mutation in
CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia
meta-signature offers a vital starting point for further studies into the
relevance of these genes (in particular CREBBP/EP300) and their concomitant
pathways as biomarkers or functional molecules in preeclampsia. This will result
in a better understanding of the molecular basis of this disease and opens up the
opportunity to develop rational therapies targeting the placental dysfunction
causal to preeclampsia.
free
free
free
