Genetically reduced soluble epoxide hydrolase activity and risk of stroke and other cardiovascular disease

TY - JOUR

T1 - Genetically reduced soluble epoxide hydrolase activity and risk of stroke and other cardiovascular disease

AU - Lee, Julie

AU - Dahl, Morten

AU - Grande, Peer

AU - Tybjaerg-Hansen, Anne

AU - Nordestgaard, Børge G

N1 - Keywords: Brain Ischemia; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Enzyme Activation; Epoxide Hydrolases; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Male; Myocardial Ischemia; Prospective Studies; Risk Factors

PY - 2010/1

Y1 - 2010/1

N2 - 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 Arg 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.

AB - 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 Arg 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.

KW - Brain Ischemia

KW - Case-Control Studies

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Enzyme Activation

KW - Epoxide Hydrolases

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Humans

KW - Male

KW - Myocardial Ischemia

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1161/STROKEAHA.109.567768

DO - 10.1161/STROKEAHA.109.567768

M3 - Journal article

C2 - 19940276

SN - 0039-2499

VL - 41

SP - 27

EP - 33

JO - Stroke

JF - Stroke

IS - 1

ER -