Involvement of ApoE E4 and H63D in sporadic Alzheimer's disease in a folate-supplemented Ontario population.
Dysregulation of iron homeostasis is implicated in Alzheimer's disease (AD). In this pilot study, common variants of the apolipoprotein E (APOE) and HFE genes resulting in the iron overload disorder of hereditary hemochromatosis (C282Y, H63D and S65C) were evaluated as factors in sporadic AD in an Ontario sample in which folic acid fortification has been mandatory since 1998. Laboratory studies also were done to search for genetic effects on blood markers of iron status, red cell folates and serum B12. Participants included 58 healthy volunteers (25 males, 33 females) and 54 patients with probable AD (20 males, 34 females). Statistical analyses were interpreted at the 95% confidence level. Contingency table and odds ratio analyses supported the hypothesis that in females of the given age range, E4 significantly predisposed to AD in the presence but not absence of H63D. In males, E4 significantly predisposed to AD in the absence of H63D, and H63D in the absence of E4 appeared protective against AD. Among E4+ AD patients, H63D was associated with significant lowering of red cell folate concentration, possibly as the result of excessive oxidative stress. However, folate levels in the lowest population quartile did not affect the risk of AD. A model is presented to explain the experimental findings.
Percy
Maire
M
Surrey Place Centre and Departments of Physiology and Obstetrics & Gynaecology, University of Toronto, Toronto, ON, Canada. maire.percy@utoronto.ca
Moalem
Sharon
S
Garcia
Angeles
A
Somerville
Martin J
MJ
Hicks
Mark
M
Andrews
David
D
Azad
Azar
A
Schwarz
Peter
P
Beheshti Zavareh
Reza
R
Birkan
Rivka
R
Choo
Clara
C
Chow
Vinca
V
Dhaliwal
Sandeep
S
Duda
Victoria
V
Kupferschmidt
Anthony L
AL
Lam
Kyla
K
Lightman
Deborah
D
Machalek
Karolina
K
Mar
Wanna
W
Nguyen
Frank
F
Rytwinski
Piotr J
PJ
Svara
Erin
E
Tran
Maithy
M
Wheeler
Kathleen
K
Yeung
Lisa
L
Zanibbi
Katherine
K
Zener
Rebecca
R
Ziraldo
Melissa
M
Freedman
Morris
M
D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008609:Mental Status Schedule; D008875:Middle Aged; D009864:Ontario; D012737:Sex Factors; D014805:Vitamin B 12 / Q000097:blood
D053327:Apolipoprotein E4; D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005492:Folic Acid; D014805:Vitamin B 12