B12 ABSORPTION, KINETICS AND TRANSCOBALAMIN GENOTYPE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vitamin B12 deficiency is common in older adults, as well as in children and young adults in developing countries. Potential consequences of B12 deficiency include megaloblastic anemia and neurological degeneration, as well as increased risk of degenerative disorders such as vascular disease, cancer, and loss of cognitive function. The primary cause of B12 deficiency is malabsorption due to pernicious anemia and atrophic gastritis. In preliminary studies, circumstantial evidence has been obtained suggesting that a common polymorphism (776CG) in the B12 transport protein, transcobalamin II, affects B12 absorption and delivery to the tissues. Consequently, this polymorphism may influence an individual's susceptibility to B12 deficiency caused by malabsorption. The goals of the present study are to assess B12 absorption and kinetics in humans, and to determine the influence of the 776CG polymorphism on these parameters. To accomplish this goal, a major technological advance available through collaboration with the Lawrence Livermore National Laboratories, called Accelerator Mass Spectrometry (AMS), will be employed. AMS provides the capacity to detect levels of carbon-14 (14C) in biological samples at attomolar concentrations. The technology is thus uniquely suited to detect the appearance of 14C in the blood, urine, and feces after oral ingestion of even small, minimally radioactive substrates. The specific aims of this proposal are to exploit AMS to assess the absorption and kinetics of 14C-labelled B12 in healthy human subjects who differ by which polymorphic variant of transcobalamin II they possess. The results of these studies will provide important basic information about the biological handling of B12 and may ultimately provide insight into the contribution of B12 deficiency to the risk of degenerative disease. Moreover, it is anticipated that the AMS technology will provide the means to develop a sensitive and specific method for assessment of B12 absorptive capacity in humans suspected of B12 malabsorption.