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. 2017 Oct 19;2(20):e95085. doi: 10.1172/jci.insight.95085

Figure 7. Gene-environment interaction model.

Figure 7

(A) Schematic diagram representing the normoglycemic condition and a proposed model in which HG results in increased ROS and reduced NO production by altering chromatin accessibility. Reduced NO is associated with increased expression of Jarid2 and its enrichment on the Notch1 locus with Setdb1. This results in repression of Notch1 and its downstream targets, culminating in congenital heart defects (highlighted by black circle). (B) Model showing gene-environment interaction between HG and Notch1 expression. In individuals without NOTCH1 mutations (red line), only severe HG crosses a threshold for congenital heart disease. Individuals with NOTCH1 mutations (blue) are a sensitized population that can cross the threshold with modest elevations in maternal blood glucose. HG, hyperglycemia; NG, normoglycemia.