Fetal alcohol spectrum disorder (FASD), including various degrees of neural developmental deficit, growth retardation, and facial dysmorphology due to exposure to alcohol during pregnancy, is a leading cause of non-genetic mental retardation.31–34 While the underlying mechanism driving FASD remains unclear,35–37 alcohol has multiple effects on methyl donors,38 which in theory, could lead to downstream epigenetic modifications,39 potentially bridging gene-environment interactions and providing a novel mechanism for FASD. Alcohol ingestion in animals has been shown to inhibit folate-mediated methionine synthesis, thereby interrupting critical methylation processes mediated through s-adenosyl methionine, the activated form of methionine and substrate for biologic methylation. Alcohol appears to interfere with the folate-methyl metabolic pathway for methyl donors by inhibiting methionine synthase and methionine adenosyl transferase. Inhibition of methionine synthesis also creates a “methylfolate trap” analogous to what occurs in vitamin B12 deficiency.38 In addition, some evidence indicates that alcohol may redirect the utilization of folate toward serine synthesis and thereby interfere with a critical function of methylene tetrahydrofolate and thymidine synthesis.40,41 The contention of alcohol-induced alteration of fetal DNA methylation has been put forward but not yet
