Differences in DNA methylation of insulin-like growth factor 2 and cadherin 13 in patients with preeclampsia

•Early-onset PE showed altered DNA methylation in placenta and umbilical cord.•There were no differences between late-onset PE and controls.•IGF-2 and cadherin 13 showed the most differential methylated CpGs.•This may even affect health and disease risks of newborns later in life. In a previous mass...

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Veröffentlicht in:Pregnancy hypertension 2020-01, Vol.19, p.150-158
Hauptverfasser: van den Berg, C.B., Herzog, E.M., Duvekot, J.J., van der Spek, P.J., Steegers, E.A.P., Stoop, M.P., Willemsen, S.P., Steegers-Theunissen, R.P.M.
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container_end_page 158
container_issue
container_start_page 150
container_title Pregnancy hypertension
container_volume 19
creator van den Berg, C.B.
Herzog, E.M.
Duvekot, J.J.
van der Spek, P.J.
Steegers, E.A.P.
Stoop, M.P.
Willemsen, S.P.
Steegers-Theunissen, R.P.M.
description •Early-onset PE showed altered DNA methylation in placenta and umbilical cord.•There were no differences between late-onset PE and controls.•IGF-2 and cadherin 13 showed the most differential methylated CpGs.•This may even affect health and disease risks of newborns later in life. In a previous mass spectrometry study of our research group, 25 proteins were found to be differentially expressed in cerebrospinal fluid of patients with preeclampsia compared to controls. The objective of the current study was to investigate DNA methylation of the genes encoding for the former mentioned proteins in an independent dataset. In a nested case-control study of the Rotterdam Periconceptional Cohort, placental tissue, umbilical cord white blood cells and human umbilical vein endothelial cells (HUVEC) were obtained of 13 patients with early-onset preeclampsia, 16 patients with late-onset preeclampsia and 83 normotensive controls (27 patients with fetal growth restriction, 20 patients with spontaneous preterm birth and 36 uncomplicated pregnancies). DNA methylation of 783 CpGs in regions of 25 genes was measured. DNA methylation of selected candidate genes in early- and late-onset preeclampsia compared to fetal growth restriction, spontaneous preterm birth and uncomplicated controls. From the 783 CpGs of the 25 selected genes, 15 CpGs were differentially methylated between early-onset preeclampsia and spontaneous preterm birth (3.80 E-5 ≤ p ≤ 0.036). Four CpGs were differentially methylated between early-onset preeclampsia and fetal growth restriction (0.0002 ≤ p ≤ 0.037) and 13 CpGs were differentially methylated between early onset preeclampsia and uncomplicated controls (0.0001 ≤ p ≤ 0.04). Differences in DNA methylation were found in placental tissue, umbilical cord white blood cells and HUVEC of patients with early onset preeclampsia compared to (un)complicated controls, but not in patients with late-onset preeclampsia. The genes showing the largest differential methylation encode insulin-like growth factor 2 binding protein and receptor and cadherin 13.
doi_str_mv 10.1016/j.preghy.2020.01.010
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DNA methylation of selected candidate genes in early- and late-onset preeclampsia compared to fetal growth restriction, spontaneous preterm birth and uncomplicated controls. From the 783 CpGs of the 25 selected genes, 15 CpGs were differentially methylated between early-onset preeclampsia and spontaneous preterm birth (3.80 E-5 ≤ p ≤ 0.036). Four CpGs were differentially methylated between early-onset preeclampsia and fetal growth restriction (0.0002 ≤ p ≤ 0.037) and 13 CpGs were differentially methylated between early onset preeclampsia and uncomplicated controls (0.0001 ≤ p ≤ 0.04). Differences in DNA methylation were found in placental tissue, umbilical cord white blood cells and HUVEC of patients with early onset preeclampsia compared to (un)complicated controls, but not in patients with late-onset preeclampsia. 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DNA methylation of selected candidate genes in early- and late-onset preeclampsia compared to fetal growth restriction, spontaneous preterm birth and uncomplicated controls. From the 783 CpGs of the 25 selected genes, 15 CpGs were differentially methylated between early-onset preeclampsia and spontaneous preterm birth (3.80 E-5 ≤ p ≤ 0.036). Four CpGs were differentially methylated between early-onset preeclampsia and fetal growth restriction (0.0002 ≤ p ≤ 0.037) and 13 CpGs were differentially methylated between early onset preeclampsia and uncomplicated controls (0.0001 ≤ p ≤ 0.04). Differences in DNA methylation were found in placental tissue, umbilical cord white blood cells and HUVEC of patients with early onset preeclampsia compared to (un)complicated controls, but not in patients with late-onset preeclampsia. 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In a previous mass spectrometry study of our research group, 25 proteins were found to be differentially expressed in cerebrospinal fluid of patients with preeclampsia compared to controls. The objective of the current study was to investigate DNA methylation of the genes encoding for the former mentioned proteins in an independent dataset. In a nested case-control study of the Rotterdam Periconceptional Cohort, placental tissue, umbilical cord white blood cells and human umbilical vein endothelial cells (HUVEC) were obtained of 13 patients with early-onset preeclampsia, 16 patients with late-onset preeclampsia and 83 normotensive controls (27 patients with fetal growth restriction, 20 patients with spontaneous preterm birth and 36 uncomplicated pregnancies). DNA methylation of 783 CpGs in regions of 25 genes was measured. DNA methylation of selected candidate genes in early- and late-onset preeclampsia compared to fetal growth restriction, spontaneous preterm birth and uncomplicated controls. From the 783 CpGs of the 25 selected genes, 15 CpGs were differentially methylated between early-onset preeclampsia and spontaneous preterm birth (3.80 E-5 ≤ p ≤ 0.036). Four CpGs were differentially methylated between early-onset preeclampsia and fetal growth restriction (0.0002 ≤ p ≤ 0.037) and 13 CpGs were differentially methylated between early onset preeclampsia and uncomplicated controls (0.0001 ≤ p ≤ 0.04). Differences in DNA methylation were found in placental tissue, umbilical cord white blood cells and HUVEC of patients with early onset preeclampsia compared to (un)complicated controls, but not in patients with late-onset preeclampsia. The genes showing the largest differential methylation encode insulin-like growth factor 2 binding protein and receptor and cadherin 13.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32007784</pmid><doi>10.1016/j.preghy.2020.01.010</doi><tpages>9</tpages></addata></record>
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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Adult
Cadherins - genetics
Case-Control Studies
CpG Islands
DNA Methylation
Endothelial Cells - metabolism
Female
Fetal Blood - cytology
Fetal Growth Retardation - genetics
Humans
HUVEC
Insulin-Like Growth Factor II - genetics
Leukocytes - metabolism
Placenta
Placenta - metabolism
Pre-Eclampsia - genetics
Preeclampsia
Pregnancy
Premature Birth - genetics
Umbilical cord white blood cells
Umbilical Veins - cytology
title Differences in DNA methylation of insulin-like growth factor 2 and cadherin 13 in patients with preeclampsia
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