title: Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Food Science and Human Nutrition Department and the General Clinical Research Center, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: von Castel-Dunwoody
authors.forename: Gail P A
authors.initials: GP
authors.lastname: Kauwell
authors.forename: Karla P
authors.initials: KP
authors.lastname: Shelnutt
authors.forename: Jaimie D
authors.initials: JD
authors.lastname: Vaughn
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Griffin
authors.forename: David R
authors.initials: DR
authors.lastname: Maneval
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Theriaque
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Bailey
mesh_terms: D000328:Adult; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D014155:Transcobalamins / Q000235:genetics* / Q000378:metabolism; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D014155:Transcobalamins; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12