Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke.
BACKGROUND
Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke.


METHODS
The GSTO1 gene was screened for variations. The effect of the detected polymorphisms on the risk of AD, VaD, and stroke was evaluated. CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype.


RESULTS
Two missense polymorphisms in exon 4 of GSTO1 (Ala140Asp and Glu155DeltaGlu) were detected and tested for their association with AD, VaD, and stroke. The Asp/Asp and Ala/Asp genotypes increased the risk of stroke (p = 0.003, OR = 2.1), and the Asp/Asp genotype increased the risk of VaD (p = 0.02, OR = 2.2). GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05). In nondemented probands CSF levels of cholesterol were increased in carriers of the Asp/Asp genotype (p = 0.004); however, in patients with manifest dementia the authors found decreased CSF levels of cholesterol in carriers of the Asp/Asp genotype (p = 0.028). Serum homocysteine levels in stroke patients were higher in carriers of at least one Asp allele (p = 0.011).


CONCLUSIONS
The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies.
Kölsch
H
H
Department of Psychiatry, University of Bonn, Germany. heike.koelsch@ukb.uni-bonn.de
Linnebank
M
M
Lütjohann
D
D
Jessen
F
F
Wüllner
U
U
Harbrecht
U
U
Thelen
K M
KM
Kreis
M
M
Hentschel
F
F
Schulz
A
A
von Bergmann
K
K
Maier
W
W
Heun
R
R
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002784:Cholesterol / Q000134:cerebrospinal fluid; D015140:Dementia, Vascular / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D005982:Glutathione Transferase / Q000235:genetics* / Q000502:physiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
D006710:Homocysteine; D002784:Cholesterol; C490476:GSTO1 protein, human; D005982:Glutathione Transferase