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Licensed Unlicensed Requires Authentication Published by De Gruyter February 26, 2008

Glutathione S-transferase variants increase susceptibility for late-onset Alzheimer's disease: association study and relationship with apolipoprotein E ɛ4 allele

Marcela A.S. Pinhel, Marcelo A. Nakazone, João C. Cação, Rafael C.O. Piteri, Raoni T. Dantas, Moacir F. Godoy, Maria R.P. Godoy, Waldir A. Tognola, Nívea D.T. Conforti-Froes and Dorotéia R.S. Souza

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 ɛ4 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 apoEɛ4 allele, while the presence of GSTT1 may indicate protection against the disease.

Clin Chem Lab Med 2008;46:439–45.


Corresponding author: Marcela Augusta de Souza Pinhel, Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto, Av. Brigadeiro Faria Lima 5416, CEP 15090-000, São José do Rio Preto, SP, Brazil Phone/Fax: +55-17-3201-5864,

Received: 2007-7-31
Accepted: 2007-12-12
Published Online: 2008-02-26
Published in Print: 2008-04-01

©2008 by Walter de Gruyter Berlin New York