title: Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy. Bernardini@Med.UniRoma2.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bellincampi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ballerini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Roberta
authors.initials: R
authors.lastname: Iori
authors.forename: Alberto
authors.initials: A
authors.lastname: Trequattrini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ciappi
authors.forename: Francesca
authors.initials: F
authors.lastname: Baldinetti
authors.forename: Paola
authors.initials: P
authors.lastname: Bossù
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
mesh_terms: 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
chemical_list: 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