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Diabetes and Vascular Disease Research
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Genetic analysis of the soluble epoxide hydrolase gene, EPHX2, in subclinical cardiovascular disease in the Diabetes Heart Study

Kathryn P Burdon

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, US.

Allison B Lehtinen

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, US.

Carl D Langefeld

Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, US.

J. Jeffrey Carr

Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, US.

Stephen S Rich

Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, US.

Barry I Freedman

Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, US.

David Herrington

Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, US.

Donald W Bowden

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, US.

Epoxide hydrolase is involved in metabolism of vasoactive and anti-inflammatory epoxyeicosatrienoic acids to their corresponding diols. Consequently, epoxide hydrolase 2 (EPHX2) is a candidate cardiovascular disease (CVD) gene. We investigated EPHX2 for association with subclinical CVD in European American (EA) and African American (AA) families from the Diabetes Heart Study. The R287Q polymorphism was associated with carotid artery calcified plaque (CarCP) in EAs. Other EPHX2 polymorphisms were associated with coronary artery calcified plaque (CorCP), CarCP or carotid artery intima-media thickness (IMT). Polymorphism rs7837347 was associated with all traits in the AAs (p=0.003, 0.001 and 0.017, respectively). Polymorphism rs7003694 displayed association with IMT (p=0.017) and, along with rs747276, a trend towards association with CorCP in diabetic EAs (p=0.057 and 0.080, respectively). These results provide additional evidence that EPHX2 contributes to the risk of subclinical CVD, although the true trait defining polymorphisms may not be identified and the effect size could be small.

Key Words: calcified plaque • cardiovascular disease • gene polymorphisms • type 2 diabetes

Diabetes and Vascular Disease Research, Vol. 5, No. 2, 128-134 (2008)
DOI: 10.3132/dvdr.2008.021
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