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NEUROLOGY 2004;63:2255-2260
© 2004 American Academy of Neurology

Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke

H. Kölsch, PhD, M. Linnebank, MD, D. Lütjohann, PhD, F. Jessen, MD, U. Wüllner, MD, U. Harbrecht, MD, K. M. Thelen, Dipl Pharm, M. Kreis, MD, F. Hentschel, MD, A. Schulz, TA, K. von Bergmann, MD, W. Maier, MD and R. Heun, MD

From the Departments of Psychiatry (Drs. Kölsch, Jessen, Schulz, Maier, and Heun), Neurology (Drs. Linnebank and Wüllner), Clinical Pharmacology (Drs. Lütjohann, Thelen, and von Bergmann), and Haemostasiology (Dr. Harbrecht), University of Bonn; and Division of Neuroradiology (Drs. Kreis and Hentschel), Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.

Address correspondence and reprint requests to Dr. Heike Kölsch, Department of Psychiatry, Sigmund-Freud-Str. 25, 53105 Bonn, Germany; e-mail: heike.koelsch{at}ukb.uni-bonn.de

Background: Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke.

Methods: The GSTO1 gene was screened for variations. The effect of the detected polymorphisms on the risk of AD, VaD, and stroke was evaluated. CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype.

Results: Two missense polymorphisms in exon 4 of GSTO1 (Ala140Asp and Glu155{Delta}Glu) were detected and tested for their association with AD, VaD, and stroke. The Asp/Asp and Ala/Asp genotypes increased the risk of stroke (p = 0.003, OR = 2.1), and the Asp/Asp genotype increased the risk of VaD (p = 0.02, OR = 2.2). GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05). In nondemented probands CSF levels of cholesterol were increased in carriers of the Asp/Asp genotype (p = 0.004); however, in patients with manifest dementia the authors found decreased CSF levels of cholesterol in carriers of the Asp/Asp genotype (p = 0.028). Serum homocysteine levels in stroke patients were higher in carriers of at least one Asp allele (p = 0.011).

Conclusion: The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies.

Received December 3, 2003. Accepted in final form August 2, 2004.




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