Glutathione S-transferase variants increase susceptibility for late-onset Alzheimer's disease: association study and relationship with apolipoprotein E epsilon4 allele.
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.
Pinhel
Marcela A S
MA
Department of Molecular Biology, São José do Rio Preto Medical School, São José do Rio Preto, SP, Brazil. marcelapinhel@yahoo.com.br
Nakazone
Marcelo A
MA
Cação
João C
JC
Piteri
Rafael C O
RC
Dantas
Raoni T
RT
Godoy
Moacir F
MF
Godoy
Maria R P
MR
Tognola
Waldir A
WA
Conforti-Froes
Nívea D T
ND
Souza
Dorotéia
D
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
D001057:Apolipoproteins E; C413545:glutathione S-transferase T1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase