Proceedings of the Nutrition Society

Symposium on ‘Micronutrients through the life cycle’

Genetic variation in genes of folate metabolism and neural-tube defect risk

Ivon J. M. van der Lindena1, Lydia A. Afmana1, Sandra G. Heila1 and Henk J. Bloma1 c2

a1 Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands


Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50–70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C677T single-nucleotide polymorphism (SNP) in the methylenetetrahydrofolate reductase (MTHFR) gene, and the observation that elevated plasma homocysteine levels are associated with NTD, research has focused on genetic variation in genes encoding for enzymes of folate metabolism and the closely-related homocysteine metabolism. In the present review relevant SNP in genes that code for enzymes involved in folate transport and uptake, the folate cycles and homocysteine metabolism are summarised and the importance of these SNP discussed in relation to NTD risk.


c1 *The other papers from this symposium were published in Proceedings of the Nutrition Society (2005), 64, 491–570.

c2 Corresponding author: Dr Henk J. Blom, fax + 31 24 3668754, email