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Title: THE SOLUBLE EPOXIDE HYDROLASE GENE HARBORS SEQUENCE VARIATIONS ASSOCIATED WITH SUSCEPTIBILITY TO AND PROTECTION FROM INCIDENT ISCHEMIC STROKE

Author
item FORNAGE, MIRIAM - UT HEALTH SCIENCE CENTER
item LEE, CRAIG - NATIONAL INST OF ENVIRON.
item DORIS, PETER - UT HEALTH SCIENCE CENTER
item Bray, Molly
item HEISS, GERARDO - UNIV. OF NORTH CAROLINA
item ZELDIN, DARRYL - NAT. INST. OF ENVIRONMENT
item BOERWINKLE, ERIC - UT HEALTH SCIENCE CENTER

Submitted to: Human Molecular Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/10/2005
Publication Date: 8/22/2005
Citation: Fornage, M., Lee, C.R., Doris, P.A., Bray, M.S., Heiss, G., Zeldin, D.C., Boerwinkle, E. 2005. The soluble epoxide hydrolase gene harbors sequence variations associated with susceptibility to and protection from incident ischemic stroke. Human Molecular Genetics. 14(19):2829-2837.

Interpretive Summary: Stroke is the leading cause of severe disability and the third leading cause of death, accounting for one of every 15 deaths in the USA. We investigated the association of DNA sequence variation in the soluble epoxide hydrolase gene (EPHX2) with stroke in African-Americans and Whites. Twelve DNA sequence variants in the EPHX2 gene were characterized in a group of 1,336 participants from the Atherosclerosis Risk in Communities (ARIC) study. In each racial group, we analyzed the relationship between the onset of stroke and EPHX2 DNA sequence variation. In African-Americans, two common EPHX2 variants with opposite relationships to stroke risk were identified. In Whites, two common forms of the EPHX2 gene showed association with stroke risk but, as in African-Americans, these relationships were in opposite direction. These findings suggest that multiple DNA sequence variants exist within or near the EPHX2 gene, with greatly contrasting relationships to the development of stroke.

Technical Abstract: Stroke is the leading cause of severe disability and the third leading cause of death, accounting for one of every 15 deaths in the USA. 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 1336 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 and others with a lower incidence.