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Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's diseaseMcCaddon, Andrew; Bleenow, Kaj; Hudson, Peter R.; Hughes, Alan; Barber, Joan; Gray, Rob; Davies, Gareth K.; Williams, John H. H.; Duguid, Jennifer; Lloyd, Alwyn; et al. (S. Karger AG, 2004)Isoforms of the vitamin B<12< carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer's disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox's F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox's F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.