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

• Published in: European journal of human genetics : EJHG Vol. 18; no. 9; pp. 1006 - 1012
• Main Authors: Yuen, Ryan KC, Peñaherrera, Maria S, von Dadelszen, Peter, McFadden, Deborah E, Robinson, Wendy P
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2010; Nature Publishing Group
• 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; Vancouver British Columbia Canada; Canada; DNA methylation; placenta; preeclampsia; prenatal diagnosis
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2010.63

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% and methylation difference >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.