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Article Abstract
Amino acid imbalance is linked to increased congenital heart disease risk. Here, we found women carrying rs2545801 C/C genotypes exhibited increased glycine levels and increased risk for atrial septal defects (ASDs) in their offspring. Elevated maternal glycine levels during the first trimester were correlated with a higher ASD risk in the offspring. Additionally, feeding pregnant mice with high-glycine chow increased ASD risk in their offspring. Mechanistically, elevated maternal glycine led to increased lysine-glycylation of lysine-688 within the TEK receptor tyrosine kinase and inhibited TEK-PI3K-AKT/FOXO1 signaling in cardiac endothelial cells. These findings indicate that lysine-glycylation exerts teratogenic effects and may be a target for ASD intervention.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226122 | PMC |
| http://dx.doi.org/10.1016/j.jacbts.2025.05.006 | DOI Listing |
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