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Am J Clin Nutr. 2005 Jun;81(6):1436-41.

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.

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1
Food Science and Human Nutrition Department and the General Clinical Research Center, University of Florida, Gainesville, FL 32611, USA.

Abstract

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 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T 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 776C-->G and MTHFR 677C-->T 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 776C-->G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.

PMID:
15941899
[Indexed for MEDLINE]
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