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ORIGINAL RESEARCH COMMUNICATION |
G polymorphism negatively affects vitamin B-12 metabolism1,2,3
1 From the Food Science and Human Nutrition Department (KMvC-D, GPAK, KPS, JDV, ERG, DRM, and LBB) and the General Clinical Research Center (DWT), University of Florida, Gainesville, FL
Background: A common genetic polymorphism [transcobalamin (TC) 776C
G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction.
Objectives: The objectives were to assess the influence of the TC 776C G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776CG and methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphisms and vitamin B-12 status on homocysteine concentrations.
Design: Healthy, nonpregnant women (n = 359; aged 20–30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776CG and MTHFR 677CT genotypes.
Results: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 ± 37 and 87 ± 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P 
0.0001) and plasma vitamin B-12 (P 0.0001) concentrations, regardless of genotype.
Conclusions: These data suggest that the TC 776CG polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.
Key Words: Holotranscobalamin • transcobalamin • polymorphisms • homocysteine • vitamin B-12
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