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Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics

European Journal of Clinical Nutrition volume 64, pages 503–509 (2010)Cite this article

Subjects

Abstract

Background/Objectives:

A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.

Subjects/Methods:

TC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60–93 years) from the Sacramento Area Latino Study on Aging (SALSA).

Results:

The distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P⩽0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 μmol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.

Conclusions:

This population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia.

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Acknowledgements

This study was financially supported by the NIH AG12975; USDA 00-35200-9073; and a Freedom to Discover pilot grant from Bristol-Meyers Squibb Foundation. We thank Teresa Ortiz, and the staff of the SALSA study for subject recruitment, phlebotomy, data collection and data management. We acknowledge the contribution of Rebecca Cotterman in blood sample processing and biochemical assessments.

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Authors and Affiliations

  1. USDA, ARS Western Human Nutrition Research Center, Davis, CA, USA

    M G Garrod & L H Allen

  2. Department of Nutrition, University of California, Davis, CA, USA

    L H Allen

  3. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    M N Haan

  4. Department of Medical Pathology and Laboratory Medicine, University of California, Sacramento, CA, USA

    R Green & J W Miller

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  1. M G Garrod
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Correspondence to J W Miller.

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The authors declare no conflict of interest.

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Contributors: MGG performed the transcobalamin genotyping assays, participated in the statistical analysis and interpretation of the data, and was responsible for drafting the article with JWM; LHA (Principal Investigator of the USDA grant 00-35200-9073) participated in the concept and design of the study and provided input into the final draft of the article; MNH (Principal Investigator of the SALSA study–the NIH Grant AG12975) participated in the concept and design of the study, was responsible for recruitment of study subjects, acquisition of blood samples, data collection and data management, participated in the statistical analysis and interpretation of the data, and provided input into the final draft of the article; RG participated in the concept and design of the study and the interpretation of the data and provided input into the final draft of the article; JWM (Principal Investigator of the Bristol-Meyers Squibb Foundation pilot grant) participated in the concept and design of the study, supervised blood processing and biochemical analyses, participated in the statistical analysis and interpretation of the data, and was responsible for drafting the article with MGG.

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Garrod, M., Allen, L., Haan, M. et al. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics. Eur J Clin Nutr 64, 503–509 (2010). https://doi.org/10.1038/ejcn.2010.20

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