title: Glutathione S-transferase variants increase susceptibility for late-onset Alzheimer's disease: association study and relationship with apolipoprotein E epsilon4 allele.
abstract: BACKGROUND
  Several factors participate in the pathogenesis of Alzheimer's disease (AD), including free radicals, which when out of balance with their antioxidant capacity contribute to the oxidative stress process and neuronal death. The glutathione S-transferase (GST) polymorphisms are associated with the organism detoxification capacity and can help with the identification of sub-groups that present susceptibility to the development of AD. The aim of this study was to analyze the association of GSTs, including GSTP1, GSTT1 and GSTM1 and apolipoprotein E (apoE) with AD and the distribution of these polymorphisms in the first-degree relatives of patients.
  
  
  METHODS
  For this, 41 patients with AD, 24 elderly without cognitive deficits (control group), 109 relatives of patients with AD and 41 relatives of controls were studied. A sample of peripheral blood was drawn for leukocyte DNA extraction. The genetic polymorphisms were analyzed by PCR-RFLP.
  
  
  RESULTS
  There was a significantly higher frequency of the 4 allele in the patients (0.21) and in their relatives (0.25) when compared to controls (0.04; p=0.01) and their relatives (0.03; p<0.0001). The V allele of the GSTP1 polymorphism was higher in patients compared to controls (0.35 and 0.19, respectively; p=0.04). In contrast, the presence of the GSTT1 polymorphism prevailed in controls (79%) and their relatives.
  
  
  CONCLUSIONS
  The V allele may be a risk factor for AD, mainly in the presence of the apoE 4 allele, while the presence of GSTT1 may indicate protection against the disease.
authors.affiliation: Department of Molecular Biology, São José do Rio Preto Medical School, São José do Rio Preto, SP, Brazil. marcelapinhel@yahoo.com.br
authors.forename: Marcela A S
authors.initials: MA
authors.lastname: Pinhel
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Nakazone
authors.forename: João C
authors.initials: JC
authors.lastname: Cação
authors.forename: Rafael C O
authors.initials: RC
authors.lastname: Piteri
authors.forename: Raoni T
authors.initials: RT
authors.lastname: Dantas
authors.forename: Moacir F
authors.initials: MF
authors.lastname: Godoy
authors.forename: Maria R P
authors.initials: MR
authors.lastname: Godoy
authors.forename: Waldir A
authors.initials: WA
authors.lastname: Tognola
authors.forename: Nívea D T
authors.initials: ND
authors.lastname: Conforti-Froes
authors.forename: Dorotéia
authors.initials: D
authors.lastname: Souza
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E; C413545:glutathione S-transferase T1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase