Placental DNA Methylation Adaptation to Maternal Glycemic Response in Pregnancy

Diabetes
Andres CardenasM F Hivert

Abstract

Maternal hyperglycemia during pregnancy is associated with excess fetal growth and adverse perinatal and developmental outcomes. Placental epigenetic maladaptation may underlie these associations. We performed an epigenome-wide association study (>850,000 CpG sites) of term placentas and prenatal maternal glycemic response 2-h post oral glucose challenge at 24-30 weeks of gestation among 448 mother-infant pairs. Maternal 2-h glycemia postload was strongly associated with lower DNA methylation of four CpG sites (false discovery rate [FDR] q <0.05) within the phosphodiesterase 4B gene (PDE4B). Additionally, three other individual CpG sites were differentially methylated relative to maternal glucose response within the TNFRSF1B, LDLR, and BLM genes (FDR q <0.05). DNA methylation correlated with expression of its respective genes in placental tissue at three out of four independent identified loci: PDE4B (r = 0.31, P < 0.01), TNFRSF1B (r = -0.24, P = 0.013), and LDLR (r = 0.32, P < 0.001). In an independent replication cohort (N = 65-108 samples), results were consistent in direction but not significantly replicated among tested CpG sites in PDE4B and TNFRSF1B Our study provides evidence that maternal glycemic response during pregn...Continue Reading

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Citations

Sep 10, 2019·American Journal of Epidemiology·Andres CardenasMarie-France Hivert
Dec 29, 2019·Diabetes·Marie-France HivertLuigi Bouchard
Jun 30, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Nora Fernandez-JimenezMarie-France Hivert
May 7, 2019·The Journal of Clinical Endocrinology and Metabolism·Virginie GilletLarissa Takser
Sep 13, 2019·Epigenetics : Official Journal of the DNA Methylation Society·E BretonL Bouchard
Oct 3, 2020·International Journal of Molecular Sciences·Valérie Gagné-OuelletLuigi Bouchard
May 8, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Hudson P SantosRebecca C Fry
Apr 16, 2020·International Journal of Molecular Sciences·Marica FranzagoLiborio Stuppia
Sep 17, 2020·Nutrients·Monika Słupecka-ZiemilskaMonika Puzianowska-Kuznicka
Jan 9, 2021·Developmental Psychobiology·Caroline TrumpffCatherine Monk
May 11, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Francisca StolzenbachBredford Kerr
Dec 19, 2020·Frontiers in Endocrinology·Maria Grazia DalfràAnnunziata Lapolla
Feb 27, 2021·Psychological Medicine·A HavdahlV Warrier
May 6, 2021·International Journal of Molecular Sciences·Mateusz KunyszDorota Darmochwał-Kolarz

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