title: DNA methylation profiles in preeclampsia and healthy control placentas.
abstract: Preeclampsia is a hypertensive disorder of pregnancy that affects 3-5% of all pregnancies. There is evidence to suggest that epigenetic mechanisms, such as DNA methylation, play a role in placental development and function. This study compared DNA methylation profiles of placentas from preeclampsia-affected pregnancies with placentas from healthy pregnancies to identify gene-specific changes in DNA methylation that may contribute to the development of preeclampsia. The methylation status of eight placental biopsies taken from preeclampsia-affected and 16 healthy pregnancies was analyzed using the Illumina Infinium Methylation 450 BeadChip array. Bisulfite pyrosequencing was used to confirm regions found to be differentially methylated between preeclampsia and healthy placentas. A total of 303 differentially methylated regions, 214 hypermethylated and 89 hypomethylated, between preeclampsia cases and controls were identified, after adjusting for gestational age (adjusted P < 0.05). Functional annotation found cell adhesion, wingless type MMTV Integration Site family member 2 (Wnt) signaling pathway, and regulation of transcription were significantly enriched in these gene regions. Hypermethylation of WNT2, sperm equatorial segment protein (SPESP1), NADPH oxidase 5 (NOX5), and activated leukocyte cell adhesion molecule (ALCAM) in preeclampsia placentas was confirmed with pyrosequencing. This study found differences in methylation in gene regions involved in cell signaling (WNT2), fertilization and implantation (SPESP1), reactive oxygen species signaling (NOX5), and cell adhesion (ALCAM). These results build on recently published studies that have reported significant differences in DNA methylation in preeclampsia placentas.
authors.affiliation: School of Medicine, Western Sydney University, Sydney, Australia;
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Yeung
authors.affiliation: School of Medicine, Western Sydney University, Sydney, Australia;
authors.forename: Christine L
authors.initials: CL
authors.lastname: Chiu
authors.affiliation: Garvan Institute of Medical Research, Sydney, Australia; and.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pidsley
authors.affiliation: Liverpool Hospital, Liverpool, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Makris
authors.affiliation: School of Medicine, Western Sydney University, Sydney, Australia;
authors.forename: Annemarie
authors.initials: A
authors.lastname: Hennessy
authors.affiliation: School of Medicine, Western Sydney University, Sydney, Australia; j.lind@westernsydney.edu.au.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D005326:Fetal Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000235:genetics; D010920:Placenta / Q000737:chemistry*; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D029589:Seminal Plasma Proteins / Q000235:genetics; D014158:Transcription, Genetic; D051154:Wnt2 Protein / Q000235:genetics; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D008565:Membrane Proteins; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; D029589:Seminal Plasma Proteins; D051154:Wnt2 Protein; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C484958:SPESP1 protein, human; C495244:WNT2 protein, human; C431571:NOX5 protein, human
keywords: deoxyribonucleic acid methylation; placenta