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 II) transports vitamin B12 to the tissues. To examine whether altered plasma transcobalamin levels are a risk factor for NTD, we determined the apo and holo form of TC II and haptocorrin (TCI+TCIII), vitamin B12 and homocysteine concentrations in the plasma of 46 mothers with NTD children, and in 73 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 related 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 individuals with low holo-tc II, low total vitamin B12 concentrations and low holo-tc II percentages. These low holo-tc II percentages are probably caused by reduced affinity of TC II for vitamin B12, which may be explained by genetic variation in the TC II gene. Vitamin B12 supplementation might therefore be warranted, in addition to folate, in the prevention of NTD.
Department of Pediatrics. Laboratory of Endocrinology and Reproduction, University Medical Center, Nijmegen, The Netherlands.
L A
LA
Afman
N M
NM
Van Der Put
C M
CM
Thomas
J M
JM
Trijbels
H J
HJ
Blom
D000328:Adult; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004587:Electrophoresis, Agar Gel; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009436:Neural Tube Defects / Q000209:etiology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012307:Risk Factors; D013223:Statistics as Topic; D014155:Transcobalamins / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism*
D014155:Transcobalamins; D006710:Homocysteine; D014805:Vitamin B 12