Gene variations in GSTM3 are a risk factor for Alzheimer's disease

Hong, G.-S.; Heun, R.; Jessen, F.; Popp, J.; Hentschel, F.; Kelemen, P.; Schulz, A.; Maier, W.; Kölsch, H.

doi:10.1016/j.neurobiolaging.2007.08.012

« Previous Next »Neurobiology of Aging
Volume 30, Issue 5 , Pages 691-696, May 2009

Gene variations in GSTM3 are a risk factor for Alzheimer's disease

G.-S. Hong
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
R. Heun
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
- Department of Psychiatry, University of Birmingham, UK
F. Jessen
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
J. Popp
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
F. Hentschel
- Division of Neuroradiology, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany
P. Kelemen
- Division of Neuroradiology, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany
A. Schulz
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
W. Maier
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
H. Kölsch
- Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
- Corresponding author. Tel.: +49 228 287 19398; fax: +49 228 287 16383.

Received 10 April 2007; received in revised form 18 July 2007; accepted 20 August 2007. published online 28 September 2007.

Abstract

Oxidative stress is a relevant pathomechanism in Alzheimer's disease (AD) and gene variations in the glutathione S-transferase M3 gene (GSTM3), involved in the detoxification of oxygen radicals, might influence the risk of AD.

We investigated the effect of three polymorphisms in GSTM3: rs1332018 (C/A); rs1799735 (del/AGG); rs7483 (G/A), on the risk of AD in 363 AD patients and 358 healthy controls.

Single marker association analyses revealed that the AGG/AGG genotype of the GSTM3 rs1799735 (del/AGG) polymorphism was associated with an increased risk of AD (p=0.05), especially in the group of APOE4-allele non-carriers (p=0.004; OR=2.07). Examination of the haplotypes identified a two-marker haplotype (C/AGG) consisting of rs1332018 (C/A) and rs1799735 (del/AGG) to increase the risk of AD (p=0.029), this effect was also most prevalent in APOE4-allele non-carriers (p=0.009; OR=1.95). The population attributable risk of this haplotype in APOE4-allele non-carriers was 32.2%.