title: Holotranscobalamin and total transcobalamin in human plasma: determination, determinants, and reference values in healthy adults.
abstract: BACKGROUND
  We developed microbiological assays (MBAs) to identify determinants and to establish reference values for cobalamin bound to transcobalamin [holotranscobalamin (holoTC)] and total TC in plasma.
  
  
  METHODS
  We captured holoTC with magnetic beads with TC antibodies and used a conventional MBA for cobalamin measurements. Total TC was determined as holoTC after TC was saturated with cyanocobalamin. The new assays were compared with published methods. Determinants and reference values were determined in 500 blood donors, ages 18-69 years.
  
  
  RESULTS
  Determination of cobalamin, holoTC, and TC by MBA required <150 microL. HoloTC and TC by MBA correlated with holoTC by RIA (r = 0.95) and TC by ELISA (r = 0.79), respectively. Between-day CVs for holoTC and total TC were 4%-9%. Women had lower holoTC than men, but only at age < or = 45 years. In multivariate regression analyses, holoTC was positively associated with age (in women only), creatinine (in men only), and plasma concentrations of total TC, folate, and cysteine, but inversely correlated with homocysteine and methylmalonic acid. For all study participants, total TC was associated with holoTC and number of TCN2 766C alleles; in female participants only, total TC was also associated with age, homocysteine, and cysteine. Reference values were 670-1270 pmol/L for TC and 42-157 pmol/L for holoTC, but they differed according to age and sex.
  
  
  CONCLUSIONS
  Our MBAs for TC and holoTC required low plasma volume and performed acceptably compared with other methods. Determinants of holoTC and TC differed between men and women and according to age. Separate reference intervals for holoTC should be considered in younger women.
authors.affiliation: Oxford Centre for Gene Function, Laboratory of Physiology, Department of Pharmacology, University of Oxford, Oxford, United Kingdom. helga.refsum@physiol.ox.ac.uk
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
authors.forename: Carole
authors.initials: C
authors.lastname: Johnston
authors.forename: Anne Berit
authors.initials: AB
authors.lastname: Guttormsen
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010949:Plasma; D012016:Reference Values; D012044:Regression Analysis; D012737:Sex Factors; D014155:Transcobalamins / Q000032:analysis*
chemical_list: D014155:Transcobalamins