Reduced vitamin B12 binding by transcobalamin II increases the risk of neural tube defects

Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTD). Homocysteine levels are elevated in mothers of NTD children , which may be due to decreased cellular vitamin B12 levels, as vitamin B12 is a cofactor for the methylation of homocysteine. Transcobalamin II (TC I I) transports vitamin B12 to the tissues. To examine whether altered plasma transcobalamin levels are a risk fatter for NTD, we determined the ape and hole form of TC II and haptocorrin (TCI + TCIII), vitamin B12 and homocyst eine concentrations in the plasma of 46 mothers with NTD children, and in 7 3 female controls. Holo-tc II levels and holo-tc II percentages (holo-tc II /total tc II) in the first quartile of the control distribution were relate d to a three-fold (OR 2.9, 95% CI 0.9-9.2) and five-fold (OR 5.0, 95% CI 1. 3-19.3) risk, respectively, for having a child with NTD, when compared with the last quartile. Homocysteine levels were significantly higher among ind ividuals with low holo-tc II, low total vitamin B12 concentrations and low holo-tc II percentages. These low holo-tc II percentages are probably cause d by reduced affinity of TC II for vitamin B12, which may be explained by g enetic variation in the TC II gene. Vitamin B12 supplementation might there fore be warranted, in addition to folate, in the prevention of NTD.