273-OR: Association of an Integrated Component of Maternal Glycemic Regulation in Pregnancy with Epigenome-Wide Cord Blood DNA Methylation

Background: Abnormal maternal glucose regulation in pregnancy has been associated with future cardiometabolic diseases in the offspring. Previous studies suggest that fetal programming is due to modulation of DNA methylation (DNAm), but they have been limited in their maternal glycemic characterization. Methods: In Gen3G, a prospective prebirth cohort, we investigated associations between an integrated component of maternal glucose regulation in pregnancy and cord blood DNAm levels in an epigenome-wide analysis at 719,558 CpG sites among 430 mother-child pairs. We used a principal component (PC) analysis to create a linear combination of multiple glucose and insulin values measured during a second trimester (24-30 weeks) oral glucose tolerance test (OGTT). We adjusted linear regression models for maternal age, parity, smoking during pregnancy, gestational week at OGTT, child sex, gestational age at delivery, and the estimated proportion of cord blood cells. Results: The first component (PC1) explained 47% of the total variation in maternal glucose and insulin values from the OGTT and was associated with methylation at cg26974062 (TXNIP) at genome-wide level significance (Bonferroni corrected P Conclusions: Among adults, blood DNAm at TXNIP has been previously associated with type 2 diabetes. Our findings suggest that an altered prenatal glucose metabolism may program dysregulation of DNAm at TXNIP across the life-course. Disclosure D. L. Juvinao-quintero: None. A. Cardenas: None. P. Perron: None. L. Bouchard: None. S. Lutz: None. M. Hivert: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-15-ACE-26 to M-F.H.)