GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: Association hypothesis for an uncommon genetic variant

Sara Piacentini, Renato Polimanti, Rosanna Squitti, Stefania Mariani, Simone Migliore, Fabrizio Vernieri, Paolo Maria Rossini, Dario Manfellotto, Maria Fuciarelli

Research output: Contribution to journalArticlepeer-review

Abstract

Glutathione S-transferases are multifunctional enzymes involved in cellular detoxification. A genetic linkage was found between Alzheimer's Disease (AD) and the chromosome 10q, where the GSTO1 and GSTO2 genes are located, leading to the hypothesis that GST Omega class (GSTO) genes may be an AD risk factor. Since it is still controversial, we decided to explore GSTO polymorphisms in Italian cohorts. We analyzed 119 AD patients and 114 healthy controls for the GSTO gene polymorphisms. In particular we investigated two common polymorphisms (GSTO1*A140D, GSTO2*N142D) and two uncommon variants (GSTO1*E155del, GSTO1*E208K) to find loci associated with AD risk. Detection of GSTO1*A140D and GSTO2*N142D was performed by PCR-RFLP, while GSTO1*E155del and GSTO1*E208K were detected using confronting two-pair primer and allele specific PCR, respectively. While GSTO1*A140D, GSTO1*E208K and GSTO2*N142D polymorphisms did not show significant outcomes, the GSTO1*E155del polymorphism is associated with AD [P= 0.003; adjusted OR = 3.70 (1.57-8.75)]. Our results suggest that GSTO1-1 plays a role in AD since the GSTO1*del155 variant is involved in changes in GSTO1-1 activities decreasing in enzyme stability. Specifically, three hypotheses may explain the role of GSTO1-1 in the pathophysiology of AD: the antioxidant activity of GSTO1-1 may protect brain tissue against oxidative stress; GSTO1-1 activity regulate interleukin-1β activation and its genetic variation may act to modulate inflammation in AD; GSTO1-1 is involved in the arsenic biotransformation pathway and gene polymorphisms may be implicated in the modulation of arsenic neurotoxicity. In conclusion, we hypothesized that GSTO1*E155del is an uncommon genetic variant associated with AD risk.

Original languageEnglish
Pages (from-to)203-207
Number of pages5
JournalNeuroscience Letters
Volume506
Issue number2
DOIs
Publication statusPublished - Jan 11 2012

Keywords

  • Glutatione S-transferases
  • GST Omega class
  • Italian population
  • Late-onset Alzheimer's disease
  • Uncommon genetic variants

ASJC Scopus subject areas

  • Neuroscience(all)

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