Published Online
on March 6, 2008

A more recent version of this article appeared on May 1, 2008

This Article Full Text (PDF) All Versions of this Article: 39/5/1593    most recent STROKEAHA.107.502179v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gschwendtner, A. Articles by Dichgans, M. Search for Related Content PubMed PubMed Citation Articles by Gschwendtner, A. Articles by Dichgans, M. Related Collections Genetics of Stroke

Submitted on August 20, 2007
Revised on October 2, 2007
Accepted on October 17, 2007

Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With an Increased Risk of Ischemic Stroke in White Europeans

Andreas Gschwendtner MD; Stephan Ripke MD; Tobias Freilinger MD; Peter Lichtner PhD; Bertram Müller-Myhsok MD; H. -Erich Wichmann PhD; Thomas Meitinger MD, PhD; and Martin Dichgans MD^*

From the Department of Neurology (A.G., T.F., M.D.), Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany; the Max-Planck-Institute of Psychiatry (S.R., B.M.-M.), Munich, Germany; the Institute of Medical Informatics (H.-E.W.), Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany; and the Institutes of Epidemiology (P.L., H.-E.W.) and Human Genetics (T.M.), GSF–National Research Institute for Environment and Health, Neuherberg, Germany.

^* To whom correspondence should be addressed. E-mail: martin.dichgans{at}med.uni-muenchen.de.

Background and Purpose—Genetic variation in the EPHX2 gene region has been reported to influence susceptibility to ischemic stroke in blacks. We assessed the role of this gene region in white Europeans and performed analyses with regard to stroke subtypes.

Methods—Twenty-six single nucleotide polymorphisms in the EPHX2 gene region were genotyped in 601 patients with ischemic stroke and 736 matched controls. Cases were subtyped according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system. Analyses were done on single markers and haplotypes using a sliding-window approach.

Results—Three single nucleotide polymorphisms showed associations with an increased risk for ischemic stroke (allelic models; all P0.01). One of them retained statistical significance after correction for multiple testing. Associations were observed with large-vessel stroke and stroke of undetermined etiology but not with other stroke subtypes.

Conclusions—Our findings confirm and extend previous studies suggesting that genetic variation in or near the EPHX2 gene contributes to the risk of ischemic stroke. This association seems to be mediated predominantly by large-vessel disease.

Key words: stroke • genetics • EPHX2

This article has been cited by other articles:

				E. Barbosa-Sicard, T. Fromel, B. Keseru, R. P. Brandes, C. Morisseau, B. D. Hammock, T. Braun, M. Kruger, and I. Fleming Inhibition of the Soluble Epoxide Hydrolase by Tyrosine Nitration J. Biol. Chem., October 9, 2009; 284(41): 28156 - 28163. [Abstract] [Full Text] [PDF]

				B. Keseru, E. Barbosa-Sicard, R. T. Schermuly, H. Tanaka, B. D. Hammock, N. Weissmann, B. Fisslthaler, and I. Fleming Hypoxia-induced pulmonary hypertension: comparison of soluble epoxide hydrolase deletion vs. inhibition Cardiovasc Res, September 4, 2009; (2009) cvp281v2. [Abstract] [Full Text] [PDF]

				M. Manhiani, J. E. Quigley, S. F. Knight, S. Tasoobshirazi, T. Moore, M. W. Brands, B. D. Hammock, and J. D. Imig Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension Am J Physiol Renal Physiol, September 1, 2009; 297(3): F740 - F748. [Abstract] [Full Text] [PDF]

				A. N. Simpkins, R. D. Rudic, D. A. Schreihofer, S. Roy, M. Manhiani, H.-J. Tsai, B. D. Hammock, and J. D. Imig Soluble Epoxide Inhibition Is Protective Against Cerebral Ischemia via Vascular and Neural Protection Am. J. Pathol., June 1, 2009; 174(6): 2086 - 2095. [Abstract] [Full Text] [PDF]

				B. Keseru, E. Barbosa-Sicard, R. Popp, B. Fisslthaler, A. Dietrich, T. Gudermann, B. D. Hammock, J. R. Falck, N. Weissmann, R. Busse, et al. Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response FASEB J, December 1, 2008; 22(12): 4306 - 4315. [Abstract] [Full Text] [PDF]