Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele.
BACKGROUND
Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD).


METHODS
We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler.


RESULTS
We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P < 0.05], but no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE epsilon4 allelic variants were at increased risk of LOAD (OR = 19.98; P < 0.0001).


CONCLUSIONS
The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE epsilon4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to beta-amyloid-mediated neurodegeneration.
Bernardini
Sergio
S
Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy. Bernardini@Med.UniRoma2.it
Bellincampi
Lorenza
L
Ballerini
Sabrina
S
Federici
Giorgio
G
Iori
Roberta
R
Trequattrini
Alberto
A
Ciappi
Fabrizio
F
Baldinetti
Francesca
F
Bossù
Paola
P
Caltagirone
Carlo
C
Spalletta
Gianfranco
G
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D012306:Risk
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human