on November 25, 2009
Published online before print November 25, 2009, doi: 10.1161/STROKEAHA.109.567768
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Submitted on September 11, 2009
From the Department of Clinical Biochemistry (J.L., M.D., B.G.N.) and The Copenhagen General Population Study (J.L., B.G.N., M.D., A.T.-H.), Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; the Departments of Cardiology (P.G.) and Clinical Biochemistry (A.T.-H.), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen City Heart Study (A.T.-H., B.G.N.), Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; and the Faculty of Health Sciences (J.L., M.D., B.G.N., A.T.-H., P.G.), University of Copenhagen, Copenhagen, Denmark. * To whom correspondence should be addressed. E-mail: brno{at}heh.regionh.dk.
Background and Purpose—The development of stroke has been linked to lowered levels of epoxyeicosatrienoic acids in the cerebral microvasculature. These substances are metabolized by the enzyme-soluble epoxide hydrolase encoded by the EPHX2 gene. We tested whether genetically reduced soluble epoxide hydrolase activity is associated with risk of ischemic stroke, myocardial infarction, and ischemic heart disease. Methods—We genotyped participants from the Copenhagen City Heart Study (n=10 352), the Copenhagen General Population Study (n=26 042), the Copenhagen Carotid Stroke Study (n=398 cases+796 control subjects), and the Copenhagen Ischemic Heart Disease Study (n=4901 cases+9798 control subjects) for the R103C, R287Q, and Arg402-403ins variants in the EPHX2 gene and recorded hospital admissions due to ischemic stroke, myocardial infarction, and ischemic heart disease. Results—The hazard/odds ratio for ischemic stroke did not differ from 1.0 for any of the EPHX2 genotypes or genotype combinations in the Copenhagen City Heart Study (P for trend=0.15 to 0.76), in the Copenhagen General Population Study (P for trend=0.75 to 0.95), and the Copenhagen Carotid Stroke Study (P for trend=0.08 to 1.00). Similar results were obtained for myocardial infarction and ischemic heart disease in the 3 studies. Conclusions—Our results show with significant power that genetically reduced soluble epoxide hydrolase activity is not a major risk factor for ischemic stroke, myocardial infarction, or ischemic heart disease in the Danish population. This suggests that the relationship between the EPHX2 gene and risk of ischemic stroke and other cardiovascular disease does not exist or its effect size is likely to be quite small.
Accepted on October 7, 2009
Genetically Reduced Soluble Epoxide Hydrolase Activity and Risk of Stroke and Other Cardiovascular Disease
Julie Lee MSc, Pharm;
Key words: epidemiology • EPHX2 • genetics of stroke