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Human Molecular Genetics Advance Access published online on August 22, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi315
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© The Author 2005. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org
Received June 23, 2005
Revised August 2, 2005
Accepted August 10, 2005

Article

The Soluble Epoxide Hydrolase Gene Harbors Sequence Variation Associated with Susceptibility to and Protection from Incident Ischemic Stroke

Myriam Fornage 1*, Craig R. Lee 2, Peter A. Doris 3, Molly S. Bray 4, Gerardo Heiss 5, Darryl C. Zeldin 6, and Eric Boerwinkle 3

1 Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center, 2121 W. Holcombe Blvd., Houston, TX 77030, Texas
2 Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, the University of North Carolina at Chapel Hill; Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina
3 Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center, Houston, Texas
4 Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
5 Department of Epidemiology, School of Public Health, the University of North Carolina at Chapel Hill
6 Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina

* To whom correspondence should be addressed.
Myriam Fornage, E-mail: myriam.fornage{at}uth.tmc.edu


  Abstract

Stroke is the leading cause of severe disability and the third leading cause of death, accounting for 1 of every 15 deaths in the United States. We investigated the association of polymorphisms in the soluble epoxide hydrolase gene (EPHX2) with incident ischemic stroke in African-Americans and Whites. Twelve single nucleotide polymorphisms (SNPs) spanning EPHX2 were genotyped in a case-cohort sample of 1,336 participants from the Atherosclerosis Risk in Communities (ARIC) study. In each racial group, Cox proportional hazard models were constructed to assess the relationship between incident ischemic stroke and EPHX2 polymorphisms. A score test method was used to investigate the association of common haplotypes of the gene with risk of ischemic stroke. In African-Americans, two common EPHX2 haplotypes with significant and opposing relationships to ischemic stroke risk were identified. In Whites, two common haplotypes showed suggestive indication of an association with ischemic stroke risk but, as in African-Americans, these relationships were in opposite direction. These findings suggest that multiple variants exist within or near the EPHX2 gene, with greatly contrasting relationships to ischemic stroke incidence; some associated with a higher incidence, others with a lower incidence.


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