Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta |
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Authors: | B.G. Janssen H.M. Byun B. Cox W. Gyselaers B. Izzi A.A. Baccarelli T.S. Nawrot |
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Affiliation: | 1. Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium;2. Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA;3. Department of Obstetrics, East-Limburg Hospital, Genk, Belgium;4. Department of Physiology, Hasselt University, Diepenbeek, Belgium;5. Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven (KULeuven), Leuven, Belgium;6. Department of Public Health & Primary Care, Occupational and Environmental Medicine, Leuven University (KULeuven), Leuven, Belgium |
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Abstract: | BackgroundEpigenetics 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).MethodsNinety 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.ResultsThe 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.ConclusionsThe 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. |
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Keywords: | Ageing Cord blood Concordance DNA methylation Epigenetics Placenta Within-placenta variation |
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