DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia

Preeclampsia and intrauterine growth restriction (IUGR) are two of the most common adverse pregnancy outcomes, but their underlying causes are mostly unknown. Although multiple studies have investigated gene expression changes in these disorders, few studies have examined epigenetic changes. Analysi...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2010-09, Vol.18 (9), p.1006-1012
Main Authors: Yuen, Ryan KC, Peñaherrera, Maria S, von Dadelszen, Peter, McFadden, Deborah E, Robinson, Wendy P
Format: Article
Language:English
Subjects:
631/208/176/1988
692/53/2421
692/699/75/243/793
692/700/1750/1747
Age
Bioinformatics
Biomarkers
Biomedical and Life Sciences
Biomedicine
Birth weight
Bisulfite
Blood pressure
CpG islands
Cytogenetics
Deoxyribonucleic acid
DNA
DNA fingerprinting
DNA Methylation
Endocrinology
Epigenetics
Female
Fetal Growth Retardation
Gene Expression
Genetics
Genomics
Human Genetics
Humans
Hypertension
Hypoxia
Investigations
Methylation
Oligonucleotide Array Sequence Analysis
Placenta
Pre-eclampsia
Pre-Eclampsia - genetics
Preeclampsia
Pregnancy
Promoter Regions, Genetic
Promoters
Tissue inhibitor of metalloproteinase 3
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Summary:Preeclampsia and intrauterine growth restriction (IUGR) are two of the most common adverse pregnancy outcomes, but their underlying causes are mostly unknown. Although multiple studies have investigated gene expression changes in these disorders, few studies have examined epigenetic changes. Analysis of the DNA methylation pattern associated with such pregnancies provides an alternative approach to identifying cellular changes involved in these disorders. We analyzed methylation of 1505 CpG sites associated with 807 genes in 26 placentas from early-onset preeclampsia (EOPET), late-onset preeclampsia, IUGR and control subjects using an Illumina GoldenGate Methylation panel. Thirty-four loci were hypomethylated (false discovery rate 10%) in the early-onset preeclamptic placentas while no and only five differentially methylated loci were found in late-onset preeclamptic and IUGR placentas, respectively. Hypomethylation of 4 loci in EOPET was further confirmed by bisulfite pyrosequencing of 26 independent placental samples. The promoter of TIMP3 was confirmed to be significantly hypomethylated in EOPET placentas ( P =0.00001). Our results suggest that gene-specific hypomethylation may be a common phenomenon in EOPET placentas, and that TIMP3 could serve as a potential prenatal diagnostic marker for EOPET.
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2010.63