|Anderson, Cindy - University Of North Dakota|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/15/2009
Publication Date: 4/24/2010
Publication URL: http://www.fasebj.org
Citation: Uthus, E.O., Anderson, C.M. 2010. Epigenetic Placental Programming of Preeclampsia. Journal of Federation of American Societies for Experimental Biology. 24:344.2.
Technical Abstract: Preeclampsia (PE) affects 8-10% of women in the US and long-term consequences include subsequent development of maternal hypertension and hypertension in offspring. As methylation patterns are established during fetal life, we focused on epigenetic alterations in DNA methylation as a plausible explanation of the heritable development of hypertension resulting from maternal PE. In this proof-of-principle study our goal was to identify promoter regions of genes that were methylated only in PE. Genome-wide CpG DNA methylation patterns were determined in placental tissue from women with normotensive pregnancy and PE (n=3/group) by using Human DNA Methylation 2.1M microarrays (NimbleGen). These arrays tile ~7000 bp upstream and ~3000 bp downstream a promoter in 100 bp segments and cover ~28000 CpG islands. Criteria for gene selection included methylation within 1000 bp upstream or downstream of the respective gene’s transcription start site. We identified 163 genes and the listing of genes was uploaded to DAVID (http://david.abcc.ncifcrf.gov) which provides functional interpretation of genes derived from genomic studies. We used a classification stringency of high to determine functional annotation clusters. Cluster 1 had an enrichment score of 5.59; this cluster contains the GO Terms of anatomical structure formation, angiogenesis, blood vessel development, vasculature development, and blood vessel morphogenesis. There are 12 genes total in this cluster; 10 of the 12 genes are common to all 5 GO Terms. This work suggests that an epigenetic mechanism may be involved in PE.