title: Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta.
abstract: BACKGROUND
  A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome.
  
  
  METHODS
  We analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing.
  
  
  RESULTS
  Preeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET) although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age.
  
  
  CONCLUSIONS
  Preeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Chu
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bunce
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Shaw
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Varsha
authors.initials: V
authors.lastname: Shridhar
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Althouse
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Carl
authors.initials: C
authors.lastname: Hubel
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Peters
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D005865:Gestational Age; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012727:Sex Characteristics