title: Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta.
abstract: BACKGROUND
  Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A, and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D-loop).
  
  
  METHODS
  Ninety individuals were randomly chosen from the ENVIRONAGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation.
  
  
  RESULTS
  The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r = 0.31 to 0.43, p ≤ 0.005, and also between the maternal and foetal sides of placental tissue (r = 0.53 to 0.72, p ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation.
  
  
  CONCLUSIONS
  The methylation levels of the subtelomeric region (D4Z4) and mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: B G
authors.initials: BG
authors.lastname: Janssen
authors.affiliation: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Byun
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Cox
authors.affiliation: Department of Obstetrics, East-Limburg Hospital, Genk, Belgium; Department of Physiology, Hasselt University, Diepenbeek, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Gyselaers
authors.affiliation: Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven (KULeuven), Leuven, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Izzi
authors.affiliation: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; Department of Public Health & Primary Care, Occupational and Environmental Medicine, Leuven University (KULeuven), Leuven, Belgium. Electronic address: bram.janssen@uhasselt.be.
authors.forename: T S
authors.initials: TS
authors.lastname: Nawrot
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D054629:Genome, Mitochondrial; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D016615:Telomere / Q000378:metabolism; D055815:Young Adult
keywords: Ageing; Concordance; Cord blood; DNA methylation; Epigenetics; Placenta; Within-placenta variation