Received on November 24, 2004
Accepted on March 7, 2005

Molecular Diagnostics and Genetics

Glutathione S-Transferase P1 *C Allelic Variant Increases Susceptibility for Late-Onset Alzheimer Disease: Association Study and Relationship with Apolipoprotein E 4 Allele

¹ Departments of Internal Medicine and Laboratory Medicine-PTV, University of Rome "Tor Vergata", Rome, Italy
² Departments of Internal Medicine and Laboratory Medicine-PTV, and Bambino Gesù-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Hospital, Rome, Italy
³ Departments of Internal Medicine and Laboratory Medicine-PTV University of Rome "Tor Vergata", Rome, Italy
⁴ ASL Città di Castello, Perugia, Italy
⁵ Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, Rome, Italy
⁶ Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, Rome, Italy, and Department of Neuroscience, University of Rome "Tor Vergata", Rome, Italy

^* To whom correspondence should be addressed. E-mail: Bernardini{at}Med.UniRoma2.it.

Background: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD).

Methods: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler.

Results: We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P <0.05], whereas we found no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE 4 allelic variants were at increased risk of LOAD (OR = 19.98; P <0.0001)

Conclusion: The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE 4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to -amyloid-mediated neurodegeneration.