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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: clinchem.2005.054619v1 52/1/129    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Refsum, H. Articles by Nexo, E. Search for Related Content PubMed PubMed Citation Articles by Refsum, H. Articles by Nexo, E. Related Collections General Clinical Chemistry

Holotranscobalamin and Total Transcobalamin in Human Plasma: Determination, Determinants, and Reference Values in Healthy Adults

¹ Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
² Institute of Medicine, Section of Pharmacology, University of Bergen, Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, Oslo, Norway.
³ Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.
⁴ Department of Clinical Biochemistry, Norrebrogade, Aarhus Sygehus, Aarhus University Hospital, Aarhus C, Denmark.

^aAddress correspondence to this author at: Oxford Centre for Gene Function, University Laboratory of Physiology, University of Oxford, Parks Rd, Oxford OX1 3P, United Kingdom. E-mail helga.refsum{at}physiol.ox.ac.uk.

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 µL. 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 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.

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