The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke.

TitleThe soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke.
Publication TypeJournal Article
Year of Publication2005
AuthorsFornage, M, Lee, CR, Doris, PA, Bray, MS, Heiss, G, Zeldin, DC, Boerwinkle, E
JournalHum Mol Genet
Volume14
Issue19
Pagination2829-37
Date Published2005 Oct 01
ISSN0964-6906
KeywordsAfrican Americans, Base Sequence, Brain Ischemia, Epoxide Hydrolases, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Middle Aged, Polymorphism, Genetic, Stroke
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.

DOI10.1093/hmg/ddi315
Alternate JournalHum. Mol. Genet.
PubMed ID16115816
PubMed Central IDPMC1343524
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
NS41466 / NS / NINDS NIH HHS / United States
R01 NS041466 / NS / NINDS NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
F32 ES012856-02 / ES / NIEHS NIH HHS / United States
HL69126 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
ES012856 / ES / NIEHS NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
F32 ES012856-03 / ES / NIEHS NIH HHS / United States
F32 ES012856-01 / ES / NIEHS NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
F32 ES012856 / ES / NIEHS NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL069126 / HL / NHLBI NIH HHS / United States