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This Article Extract Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Morkbak, A. L. Articles by Nexø, E. Search for Related Content PubMed Articles by Morkbak, A. L. Articles by Nexø, E. Related Collections Nutrition Endocrinology and Metabolism

The authors of the article cited above respond:

Department of Clinical Biochemistry, Aarhus Sygehus, Aarhus University Hospital, 8000 Aarhus, Denmark.

^aAddress correspondence to this author at: Department of Clinical Biochemistry, Aarhus Sygehus, Aarhus University Hospital, 8000 Aarhus, Denmark.

To the Editor:

Dr. Carmel was the first to report that total haptocorrin (HC) and cobalamins are related and that this relationship may be associated with the occurrence of heterozygosity for HC deficiency (1). The rarity of HC deficiency, however, suggests that this explanation is probably incomplete. Furthermore, a continuous relationship exists between HC and cobalamins, not the stepwise one that would occur if simple gene dosage were the mechanism. Therefore we—and Carmel, according to his letter—believe that the genetic factors determining HC concentrations are more complex. Obviously, further studies are needed to give a clear picture of the relationship between such factors and the concentration of HC. So far, Carmel has demonstrated a relationship between HC and cobalamins (correlation not indicated; P = 0.003, n = 182), a relationship further substantiated by our study (r²=0.4, P <0.0001, n = 402), which employed an optimized method using deglycosylation to ensure that HC from different samples are measured on an equimolar basis (2).

Our data indicating that HC concentrations increase in vitamin B₁₂ deficient individuals who are treated with vitamin B₁₂ supplementation lead us to propose that the HC concentration is influenced not only by genetic factors but also by vitamin B₁₂ status (3). Carmel challenges this conclusion, raising some relevant issues, which we address below:

Could the observed increase in HC be caused by methodological pitfalls, such as the spurious introduction of apoHC by in vitro release of HC from leukocytes during serum analysis?

We do not believe that this is the case because serum (vegan population) was analyzed both before and after treatment with vitamin B₁₂. Furthermore, no alteration was observed in the leukocytes as a consequence of treatment.

Is the observed increase in HC common in the vegan population as a whole, or is it driven by an increase in just a few individuals?

That this response is common in the vegan population is demonstrated by our finding that 55 of 63 individuals in our vegan sample population had increased total HC after treatment with 5 mg vitamin B₁₂ (Fig. 1 ).

View larger version (14K): [in this window] [in a new window]   Figure 1. Increase in total HC in the group of deficient individuals treated with vitamin B12 (5 mg per day; n = 63) and placebo (n = 85).

Is it possible that everyone would show an increase in HC if given a megadose of vitamin B₁₂?

We cannot conclude whether treatment with 5 mg vitamin B₁₂ per day would lead to increased total HC in individuals without as well as those with vitamin B₁₂ deficiency. However, increased HC in response to vitamin B₁₂ supplementation in individuals without vitamin B₁₂ deficiency would still indicate a relationship between vitamin B₁₂ status and HC concentration.

Although we have further scrutinized our results in the light of the comments from Carmel, we still find that the most obvious explanation for our findings is that the concentration of HC is influenced by the vitamin B₁₂ status of the patient. The issue has important implications for the interpretation of low cobalamin in relation to low HC concentrations in patients undergoing examination for vitamin B₁₂ deficiency. If genetic factors were the only regulators of the HC concentration, the physician could decide that the low concentration of cobalamins reflected an inherited low HC. If HC is regulated by the vitamin B₁₂ status in addition to the genetic factors, as suggested by us, such a patient should always undergo further analysis to rule out a deficiency state.

References

1. Carmel R, Brar S, Frouhar Z. Plasma total transcobalamin I. Ethnic/racial patterns and comparison with lactoferrin. Am J Clin Pathol 2001;116:576-580.[CrossRef][ISI][Medline] [Order article via Infotrieve]
2. Morkbak AL, Pedersen JF, Nexo E. Glycosylation independent measurement of the cobalamin binding protein haptocorrin. Clin Chim Acta 2005;356:184-190.[CrossRef][ISI][Medline] [Order article via Infotrieve]
3. Morkbak AL, Hvas AM, Lloyd-Wright Z, Sanders TA, Bleie O, Refsum H, et al. Effect of vitamin B12 treatment on haptocorrin. Clin Chem 2006;52:1104-1111.[Abstract/Free Full Text]

This Article Extract Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Morkbak, A. L. Articles by Nexø, E. Search for Related Content PubMed Articles by Morkbak, A. L. Articles by Nexø, E. Related Collections Nutrition Endocrinology and Metabolism