Effect of TCN2 776C>G on vitamin B12 cellular availability in end-stage renal disease patients

Background. Transcobalamin II is a serum protein that transports vitamin B-12 from the intestine to the tissues. This complex, holo-transcobalamin II, may reflect vitamin B-12 availability in the body. Conflicting data exist with regard to the effect of a polymorphism in the gene coding for transcobalamin II, TCN2 776C>G, on transcobalamin II levels in the general population, which in turn may affect holo-transcobalamin II, vitamin B-12 , as well as total homocysteine (tHcy) plasma levels. The effect of TCN2 776C>G on vitamin B-12 cellular availability in dialysis patients is unknown. Methods. We examined the effect of TCN2 776C>G on holo-transcobalamin II, vitamin B-12 , and tHcy plasma concentrations in 120 dialysis patients. Results. Holo-transcobalamin II levels were normal or supranormal in all patients and showed a linear association with albumin (r = 0.205, P = 0.025) and with vitamin B-12 (r = 0.778, P = 0.001), but not with age, creatinine, body mass index, tHcy, ln-tHcy, vitamin B-6 , plasma folate, and red blood cell folate concentration. TCN2 776C>G showed no effect on holo-transcobalamin II, vitamin B-12 , and tHcy concentration [one-way analysis of variance (ANOVA), post-hoc Scheffe test]. Multiple linear regression analyses showed that albumin and B-12 are independently associated with holo-transcobalamin II, whereas TCN2 776C>G and MTHFR 677C>T had no effect. Independent predictors of ln-tHcy included creatinine, red blood cell folate, and the MTHFR 677TT genotype. There was also an effect of the TCN2 776CC genotype on ln-tHcy levels in this multivariate analysis, however, that deserves cautious interpretation because there was no effect of TCN2 genotypes by ANOVA and Scheffe test [median ln-tHcy concentrations according to TCN2 genotypes (mumol/L): CC, 3.22; CG, 3.30; GG, 3.23]. Conclusion. TCN2 776C>G does not influence holo-transcobalamin II or vitamin B-12 levels, and has no major effect on tHcy concentrations of end-stage renal disease patients.