Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans

• Published in: Neuroscience letters Vol. 344; no. 3; pp. 189 - 192
• Main Authors: Guéant-Rodriguez, R.M., Rendeli, C., Namour, B., Venuti, L., Romano, A., Anello, G., Bosco, P., Debard, R., Gérard, P., Viola, M., Salvaggio, E., Guéant, J.L.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 03-07-2003; Elsevier
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics; Adolescent; Biological and medical sciences; Child; Child, Preschool; Diseases of the osteoarticular system; Diseases of the spine; Female; Ferredoxin-NADP Reductase - genetics; Humans; Infant; Male; Medical sciences; Methionine synthase; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Neural tube defect; Neural Tube Defects - genetics; Oxidoreductases Acting on CH-NH Group Donors - genetics; Polymorphism, Genetic; Risk Factors; Single nucleotide polymorphism; Transcobalamin; Transcobalamins - genetics; Transcobalamin; Single nucleotide polymorphism; Methionine synthase; Neural tube defect; Human; O-Acetylhomoserine (thiol)-lyase; Enzyme; Pathogenesis; Transferases; Diseases of the osteoarticular system; Lyases; Spine disease; Congenital disease; Genetic determinism; Spina bifida; Neural tube; [Methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing); Methyltransferases; Malformation; Carbon-oxygen lyases; Polymorphism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(03)00468-3

The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine,
transcobalamin (
TC),
methionine
synthase (
MTR) and
MTR
reductase (
MTRR), combined or not with
methylenetetrahydrofolate
reductase (
MTHFR), with the risk of having neural tube defect in 40 children with spina bifida and 58 matched controls from South Italy.
MTR
2756
AG/GG,
TC
777
CG/GG
/MTHFR
677
CC and
MTRR
66
GG
/MTHFR
677
CC genotypes increased the risk with odds ratios of 2.6 (
P=0.046), 2.4 (
P=0.028) and 4.5 (
P=0.023), respectively. In contrast,
MTHFR
677
TT was protective (odds ratio=0.11,
P=0.009). In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.