title: Transcobalamin polymorphism 67A->G, but not 776C->G, affects serum holotranscobalamin in a cohort of healthy middle-aged men and women.
abstract: Two polymorphic variants in the gene coding for transcobalamin II (TCN2), TCN2 776C- > G and TCN2 67A- > G, may alter serum holotranscobalamin (holoTC), which in turn may affect cellular uptake of cobalamin (Cbl) and thereby Cbl status indicators. We studied the effects of TCN2 776C- > G and TCN2 67A- > G on blood concentrations of holoTC, Cbl, methylmalonic acid (MMA), and total homocysteine (tHcy) in 2411 individuals (50-64 y) that had been selected on the basis of these TCN2 genotypes from 10601 Norwegian inhabitants. The serum holoTC concentration was lower in TCN2 67AG (55 ± 0.75 pmol/L) and 67GG (48 ± 2.14 pmol/L) than in 67AA (62 ± 0.67 pmol/L) (P < 0.001) but did not differ among TCN2 776C- > G genotypes. The polymorphisms interacted as serum holoTC determinants (P = 0.001) and the presence of TCN2 67AG and GG in strata of 776CC and CG, but not 776GG, increased the risk of having serum holoTC < 45.6 pmol/L [tertile 1 vs. tertiles 2 and 3: OR = 2.5 (95% CI 1.8-3.5) for 67AG; OR = 5.7 (95% CI 3.5-9.1) for 67GG in 776CC; OR = 2.1 (95% CI 1.6-2.9) for 67AG; and OR = 4.5 (95% CI 2.4-8.2) for 67GG in 776CG; all P < 0.001]. Plasma MMA, tHcy, and Cbl were not affected by either polymorphism. In summary, serum holoTC, but not plasma Cbl, MMA, or tHcy, varied according to TCN2 67A- > G genotypes. It remains to be determined whether this polymorphic effect on serum holoTC alters its diagnostic utility as Cbl status indicator.
authors.affiliation: Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. bettina.marie.riedel@helse-bergen.no
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Riedel
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Ase
authors.initials: A
authors.lastname: Fredriksen
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.forename: Jørn
authors.initials: J
authors.lastname: Schneede
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexø
authors.forename: Geir
authors.initials: G
authors.lastname: Hoff
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
mesh_terms: D000483:Alleles; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009664:Norway; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012737:Sex Factors; D014155:Transcobalamins / Q000032:analysis* / Q000235:genetics*; D014806:Vitamin B 12 Deficiency / Q000097:blood
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D014155:Transcobalamins