F. Namour et al., Transcobalamin codon 259 polymorphism in HT-29 and Caco-2 cells and in Caucasians, relation to transcobalamin and homocysteine concentration in blood, BLOOD, 97(4), 2001, pp. 1092-1098
Transcobalamin (TC) is the plasma transporter that delivers vitamin B-12 to
cells. We have already reported that HT-29 and Caco-2 cells secrete differ
ent TC variants. HT-29 secretes 2 TC isoproteins (codon 259-Pro/Arg [259-P/
R]), exhibiting unequal concentrations (TC 259-P > TC 259-R), and Caco-2 ce
lls only secrete the phenotype 259-R, We investigated the relation between
phenotypic and genetic TC polymorphism in HT-29 cells transfected with Caco
-2 TC complementary DNA and in 159 healthy Caucasians. We found that codon
259-R is buried and, thus, the genetic polymorphism provides no explanation
why the TCs from HT-29 and Caco-2 cells have different isoelectric points
in nondenaturing isoelectric focusing (IEF), The newly translated TC in MT-
29 cells from the Caco-2 complementary DNA recombinant plasmid had the same
isoelectric point as the TC constitutively expressed in MT-29 cells, sugge
sting that TC phenotypic variability involves a specific cell folding of th
e protein. The codon 259 polymorphism was found to have a biallelic distrib
ution: homozygotes P = 34.6%, heterozygotes R/P = 47.8%, and homozygotes R
= 17.6%. In heterozygous samples, the IEF showed that the TC 259-P/TC 259-R
ratio = 1.6 The blood apo-TC concentration of 259-P homozygous Caucasians
was significantly higher than that of homozygous 259-R (P < .0001) and hete
rozygous (P < .0006) Caucasians, The heterozygotes 259-R/P had homocysteine
concentration significantly higher than the homozygotes 259-R and 259-P (P
= .02 and P = .01, respectively). In conclusion, TC codon-259 polymorphism
affects TC plasma concentration and may interfere in vitamin B-12 cellular
availability and homocysteine metabolism.