Zain Awamleh1, Darci T Butcher2, Anthony Hanley3, Ravi Retnakaran4, Larissa Haertle5, Thomas Haaf6, Jill Hamilton7, Rosanna Weksberg8. 1. Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada. 2. Head of Molecular Genomics, Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. 3. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. 4. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 5. Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany; Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany. 6. Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany. 7. Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address: jill.hamilton@sickkids.ca. 8. Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, Ontario, Canada. Electronic address: rweksb@sickkids.ca.
Abstract
BACKGROUND: Fetal exposure to maternal GDM increases offspring risk for adult-onset metabolic syndromes. Epigenetic modifications such as DNA methylation are modulators for fetal metabolic programming and susceptibility to adult-onset disease. This study investigates genome-wide DNA methylation in GDM exposed cord blood and placenta. METHODS: Oral glucose tolerance testing between 24 and 28 weeks of pregnancy was used to determine severity of glucose intolerance. We measured DNA methylation (DNAm) using the Illumina Infinium 450 K array in 42 fetal cord blood and 36 placenta samples. RESULTS: We identified 662 and 99 CpG sites in GDM placenta and cord blood, respectively at p-value <0.01 and a methylation difference >5% after adjustment for confounders. Annotated sites for AHRR and PTPRN2 were common to cord blood and placenta. Adding published GDM cord blood DNAm data we segregated patients based on treatment (Diet Only vs. +Insulin) and identified altered CpG sites to be unique to each GDM treatment group. CONCLUSION: Consistency in findings with other studies provides evidence for the role of DNAm in placental and fetal responses to hyperglycemia. However, segregating DNAm analysis of GDM samples based on treatment may help delineate whether observed DNAm alterations are reflective of adaptive responses or treatment effects in utero.
BACKGROUND: Fetal exposure to maternal GDM increases offspring risk for adult-onset metabolic syndromes. Epigenetic modifications such as DNA methylation are modulators for fetal metabolic programming and susceptibility to adult-onset disease. This study investigates genome-wide DNA methylation in GDM exposed cord blood and placenta. METHODS: Oral glucose tolerance testing between 24 and 28 weeks of pregnancy was used to determine severity of glucose intolerance. We measured DNA methylation (DNAm) using the Illumina Infinium 450 K array in 42 fetal cord blood and 36 placenta samples. RESULTS: We identified 662 and 99 CpG sites in GDM placenta and cord blood, respectively at p-value <0.01 and a methylation difference >5% after adjustment for confounders. Annotated sites for AHRR and PTPRN2 were common to cord blood and placenta. Adding published GDM cord blood DNAm data we segregated patients based on treatment (Diet Only vs. +Insulin) and identified altered CpG sites to be unique to each GDM treatment group. CONCLUSION: Consistency in findings with other studies provides evidence for the role of DNAm in placental and fetal responses to hyperglycemia. However, segregating DNAm analysis of GDM samples based on treatment may help delineate whether observed DNAm alterations are reflective of adaptive responses or treatment effects in utero.
Authors: Rebekka M Koeck; Florence Busato; Jorg Tost; Dimitri Consten; Jannie van Echten-Arends; Sebastiaan Mastenbroek; Yvonne Wurth; Sylvie Remy; Sabine Langie; Tim S Nawrot; Michelle Plusquin; Rossella Alfano; Esmée M Bijnens; Marij Gielen; Ron van Golde; John C M Dumoulin; Han Brunner; Aafke P A van Montfoort; Masoud Zamani Esteki Journal: NPJ Genom Med Date: 2022-06-29 Impact factor: 6.083
Authors: Rebeca Fernández-Carrión; Jose V Sorlí; Oscar Coltell; Eva C Pascual; Carolina Ortega-Azorín; Rocío Barragán; Ignacio M Giménez-Alba; Andrea Alvarez-Sala; Montserrat Fitó; Jose M Ordovas; Dolores Corella Journal: Biomedicines Date: 2021-12-31