Isoelectrofocusing phenotype and relative concentration of transcobalamin II isoproteins related to the codon 259 Arg/Pro polymorphism.

We investigated transcobalamin II (TC) isoelectrofocusing (IEF) phenotype and codon 259 polymorphism, in Caco-2 and HT-29 cells and in blood drawn from 39 healthy Caucasians. Caco-2 cells expressed a single TC variant (259-Arg), while HT-29 cells expressed TC with either Arg or Pro at codon 259 and exhibited two isoproteins in IEF with urea, but only one in IEF without urea. Among the Caucasians, 7 subjects expressed the TC 259-Arg variant, 10 the 259-Pro variant, and 22 were heterozygous. The TC 259-Pro isoprotein issued from HT-29 cells and heterozygous caucasian sera, was, respectively, 2. 4-fold and 1.6-fold higher than the TC 259-Arg isoprotein. Apo-TC and vitamin B12 serum concentrations in 259-Pro homozygotes were, respectively, 1.7 and 1.4-fold higher than those in 259-Arg homozygotes (p<0.005 and p=0.05). In conclusion, the 259-Arg/Pro polymorphism yields two TC variants only titratable in denaturing conditions and affects the blood level of both Apo-TC and vitamin B12. Copyright 1998 Academic Press.