on August 23, 2007
Published online before print August 23, 2007, doi: 10.1161/STROKEAHA.107.484162
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Submitted on February 1, 2007
From the Departments of Psychiatry (H.K.), and Neuropathology (S.L., O.D., D.R.T.), University of Bonn, Bonn, Germany; the Department of Pathology (M.O.), Municipal Hospital Offenbach am Main, Offenbach am Main, Germany; the Department of Biochemistry (G.B.), University of Leipzig, Leipzig, Germany; and the Donald W. Reynolds Center on Aging (W.S.T.G.), UAMS, Geriatric Research Education and Clinical Center, Veterans' Affairs Medical Center, Little Rock, Ark. * To whom correspondence should be addressed. E-mail: Didithal{at}aol.com.
Background and Purpose—Glutathione S-transferase omega-1 is a multifunctional enzyme. The Asp/Asp genotype of the Ala140Asp polymorphism of the GSTO1 gene has been alleged to increase the risk of vascular dementia. The objective of this study is to address the question of whether common vessel disorders known to cause vascular dementia are modified in their severity by this polymorphism. Methods—The severity and expansion of atherosclerosis in the circle of Willis vessels, cerebral small vessel disease, and cerebral amyloid angiopathy were studied in a sample of 79 autopsy cases. Genotyping of the GSTO1 Ala140Asp polymorphism as well as immunohistochemistry for glutathione S-transferase omega-1 was performed. Results—Carriers of the GSTO1 Asp/Asp genotype presented with more severe and widespread atherosclerosis than noncarriers. However, there was no effect on small vessel disease expansion and cerebral amyloid angiopathy severity. Immunohistochemically, we detected interleukin-1 Conclusions—The GSTO1 Asp/Asp genotype presumably modulates the severity and expansion of atherosclerosis in the circle of Willis. The cellular colocalization of glutathione S-transferase omega-1 and interleukin-1
Revised on February 23, 2007
Accepted on March 20, 2007
Association of the Glutathione S-transferase Omega-1 Ala140Asp Polymorphism With Cerebrovascular Atherosclerosis and Plaque-Associated Interleukin-1
Heike Kölsch PhD; 
Expression
expressing macrophages in the lipid core of atherosclerosis plaques exhibiting glutathione S-transferase omega-1-positive material. GSTO1 Asp/Asp carriers showed larger areas of atherosclerosis plaques containing interleukin-1-positive material than carriers of the GSTO1 Ala-allele. suggests a functional interaction between both proteins which in part might explain the function of glutathione S-transferase omega-1 in the pathogenesis of cerebral atherosclerosis.
Key words: atherosclerosis • cerebral arteries • GSTO1-1