Diana L Juvinao-Quintero1, Anne P Starling2, Andres Cardenas3, Camille E Powe4,5,6, Patrice Perron7,8, Luigi Bouchard7,9,10, Dana Dabelea2, Marie-France Hivert1,4. 1. Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA 02215, USA. 2. Department of Epidemiology & Lifecourse Epidemiology of Adiposity & Diabetes (LEAD) Center, Colorado School of Public Health, University of Colorado, Anschutz Medical Campus, CO 80045, USA. 3. Division of Environmental Health Sciences, School of Public Health & Center for Computational Biology, University of California, Berkeley, CA 94720-7360, USA. 4. Diabetes Unit, Massachusetts General Hospital, Boston, MA 02114, USA. 5. Harvard Medical School, Boston, MA 02115, USA. 6. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. 7. Centre de Recherche du CHUS, Sherbrooke, QC J1H 5N4, CA. 8. Department of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. 9. Department of Medical Biology, CIUSSS Saguenay-Lac-Saint-Jean, Hôpital Universitaire de Chicoutimi, Saguenay, QC G7H 5H6, Canada. 10. Department of Biochemistry & Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Abstract
Background: Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). Materials & methods: We tested associations between maternal HbA1c and cord blood DNAm among 412 mother-child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Results: Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 × 10-11) near URGCP. Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. Conclusion: We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at URGCP, a gene related with inflammatory pathways.
Background: Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). Materials & methods: We tested associations between maternal HbA1c and cord blood DNAm among 412 mother-child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Results: Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 × 10-11) near URGCP. Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. Conclusion: We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at URGCP, a gene related with inflammatory pathways.
Entities:
Keywords:
DNA methylation; HbA1c; Mendelian randomization; cord blood; hyperglycemia; pregnancy
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