title: Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease.
abstract: 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.
authors.affiliation: University of Wales College of Medicine, Division of General Practice, Wrexham, UK. andrew@mccaddon.demon.co.uk
authors.forename: Andrew
authors.initials: A
authors.lastname: McCaddon
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Peter
authors.initials: P
authors.lastname: Hudson
authors.forename: Alan
authors.initials: A
authors.lastname: Hughes
authors.forename: Joan
authors.initials: J
authors.lastname: Barber
authors.forename: Rob
authors.initials: R
authors.lastname: Gray
authors.forename: Gareth
authors.initials: G
authors.lastname: Davies
authors.forename: John H H
authors.initials: JH
authors.lastname: Williams
authors.forename: Jennifer
authors.initials: J
authors.lastname: Duguid
authors.forename: Alwyn
authors.initials: A
authors.lastname: Lloyd
authors.forename: Steve
authors.initials: S
authors.lastname: Tandy
authors.forename: Marge
authors.initials: M
authors.lastname: Everall
authors.forename: Howard
authors.initials: H
authors.lastname: Cattell
authors.forename: Anne
authors.initials: A
authors.lastname: McCaddon
authors.forename: Dick
authors.initials: D
authors.lastname: Ellis
authors.forename: Mona
authors.initials: M
authors.lastname: Palmer
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Carl-Gerhard
authors.initials: CG
authors.lastname: Gottfries
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Lars
authors.initials: L
authors.lastname: Rymo
authors.forename: Björn
authors.initials: B
authors.lastname: Regland
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D016019:Survival Analysis; D014805:Vitamin B 12 / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D014805:Vitamin B 12