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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
Published/Copyright: February 26, 2008
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 46 Issue 4

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.

Keywords: Alzheimer's disease; apolipoprotein E; glutathione S-transferase; oxidative stress; polymorphisms
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

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https://doi.org/10.1515/CCLM.2008.102
Keywords for this article
Alzheimer's disease; apolipoprotein E; glutathione S-transferase; oxidative stress; polymorphisms

Articles in the same Issue

  1. Editorial
  2. Improving clinicians understanding of lipoprotein sub-fractions through new technology
  3. Review
  4. Free fatty acids as a cardiovascular risk factor
  5. Opinion Papers
  6. Pharmacy-based laboratory services: past or future and risk or opportunity?
  7. Standards of practice and uniformity in references style
  8. Genetics and Molecular Diagnostics
  9. Glutathione S-transferase variants increase susceptibility for late-onset Alzheimer's disease: association study and relationship with apolipoprotein E ɛ4 allele
  10. The D allele of angiotensin I-converting enzyme gene insertion/deletion polymorphism is associated with the severity of atherosclerosis
  11. The apolipoprotein A5 gene –1131T→C polymorphism affects vitamin E plasma concentrations in type 2 diabetic patients
  12. Cell lines that express membrane-associated DNA for anti-DNA antibody detection
  13. Certification of reference materials for detection of the human prothrombin gene G20210A sequence variant
  14. Caspase-3 gene transfected with LIGHT gene: can it be used for therapy of human hepatocellular carcinoma?
  15. Performance characteristics of a real-time RT-PCR assay for quantification of hepatitis C virus RNA in patients with genotype 1 and 2 infections
  16. Apolipoprotein E polymorphisms in Mexican patients with coronary artery disease
  17. A new single nucleotide polymorphism genotyping method based on gap ligase chain reaction and a microsphere detection assay
  18. General Clinical Chemistry and Laboratory Medicine
  19. PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol
  20. Evaluation of oxidative stress and inflammation in obese adults with metabolic syndrome
  21. Sex differences in adenosine deaminase activity of stroke patients
  22. Serum levels of the osteoprotegerin, receptor activator of nuclear factor κ-B ligand, metalloproteinase-1 (MMP-1) and tissue inhibitors of MMP-1 levels are increased in men 6 months after acute myocardial infarction
  23. Gelatinase matrix metalloproteinase (MMP)-2 and MMP-9 of the umbilical cord blood in preeclampsia
  24. Association between plasma alkaline phosphatase and C-reactive protein in Hong Kong Chinese
  25. Carbonylation of platelet proteins occurs as consequence of oxidative stress and thrombin activation, and is stimulated by ageing and type 2 diabetes
  26. An automated assay of urinary alanine aminopeptidase activity
  27. Non-high-density lipoprotein cholesterol levels and recent involuntary weight gain among asymptomatic female subjects
  28. Reference Values
  29. Reference intervals for circulating angiogenic cytokines
  30. Hematological parameters in preterm infants from birth to 16 weeks of age with reference to iron balance
  31. Influence of hydroxyethyl starch (6% HES 130/0.4) administration on hematology and clinical chemistry parameters
  32. Letters to the Editor
  33. Eosinophilic cationic protein in bronchoalveolar lavage fluid of lung transplant patients
  34. Simple human error in data reading and expression in clinical chemistry
  35. Reply to Dr. Park's letter
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  38. Implementation of standardization of HbA1c measurement Summary of the meeting with manufacturers held in Milan, Italy, December 12, 2007
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  40. 3rd International Conference on Dipeptidyl Peptidase and Related Proteins Antwerp, Belgium, April 23–25, 2008
  41. Seventh International Symposium on Molecular Diagnostics Graz, Austria, May 22–24, 2008
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