Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease.
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.
McCaddon
Andrew
A
University of Wales College of Medicine, Division of General Practice, Wrexham, UK. andrew@mccaddon.demon.co.uk
Blennow
Kaj
K
Hudson
Peter
P
Hughes
Alan
A
Barber
Joan
J
Gray
Rob
R
Davies
Gareth
G
Williams
John H H
JH
Duguid
Jennifer
J
Lloyd
Alwyn
A
Tandy
Steve
S
Everall
Marge
M
Cattell
Howard
H
McCaddon
Anne
A
Ellis
Dick
D
Palmer
Mona
M
Bogdanovic
Nenad
N
Gottfries
Carl-Gerhard
CG
Zetterberg
Henrik
H
Rymo
Lars
L
Regland
Björn
B
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*
D001057:Apolipoproteins E; D014805:Vitamin B 12