Folate-mediated one-carbon metabolism and neural tube defects: Balancing genome synthesis and gene expression
Article first published online: 26 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
Birth Defects Research Part C: Embryo Today: Reviews
Volume 81, Issue 3, pages 183–203, September 2007
How to Cite
Beaudin, A. E. and Stover, P. J. (2007), Folate-mediated one-carbon metabolism and neural tube defects: Balancing genome synthesis and gene expression. Birth Defects Research Part C: Embryo Today: Reviews, 81: 183–203. doi: 10.1002/bdrc.20100
- Issue published online: 26 OCT 2007
- Article first published online: 26 OCT 2007
Neural tube defects (NTDs) refer to a cluster of neurodevelopmental conditions associated with failure of neural tube closure during embryonic development. Worldwide prevalence of NTDs ranges from approximately 0.5 to 60 per 10,000 births, with regional and population-specific variation in prevalence. Numerous environmental and genetic influences contribute to NTD etiology; accumulating evidence from population-based studies has demonstrated that folate status is a significant determinant of NTD risk. Folate-mediated one-carbon metabolism (OCM) is essential for de novo nucleotide biosynthesis, methionine biosynthesis, and cellular methylation reactions. Periconceptional maternal supplementation with folic acid can prevent occurrence of NTDs in the general population by up to 70%; currently several countries fortify their food supply with folic acid for the prevention of NTDs. Despite the unambiguous impact of folate status on NTD risk, the mechanism by which folic acid protects against NTDs remains unknown. Identification of the mechanism by which folate status affects neural tube closure will assist in developing more efficacious and better targeted preventative measures. In this review, we summarize current research on the relationship between folate status and NTDs, with an emphasis on linking genetic variation, folate nutriture, and specific metabolic and/or genomic pathways that intersect to determine NTD outcomes. Birth Defects Research (Part C) 81:183–203, 2007. © 2007 Wiley-Liss, Inc.