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(Circulation. 2004;109:335-339.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Polymorphism of the Soluble Epoxide Hydrolase Is Associated With Coronary Artery Calcification in African-American Subjects

The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Myriam Fornage, PhD; Eric Boerwinkle, PhD; Peter A. Doris, PhD; David Jacobs, PhD; Kiang Liu, PhD; Nathan D. Wong, PhD

From the Institute of Molecular Medicine for the Prevention of Human Diseases (M.F., P.A.D.) and Human Genetics Center (E.B.), University of Texas Health Science Center, Houston, Tex; Division of Epidemiology (D.J.), University of Minnesota, Minneapolis, Minn; Northwestern University Medical School (K.L.), Chicago, Ill; and Heart Disease Prevention Program (N.D.W.), University of California, Irvine, Calif.

Correspondence to Myriam Fornage, PhD, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, 2121 W. Holcombe Blvd, Houston, TX 77030. E-mail myriam.fornage{at}uth.tmc.edu

Received July 21, 2003; revision received October 2, 2003; accepted October 9, 2003.

Background— Modulation of endogenous epoxide levels by soluble epoxide hydrolase (sEH) in the endothelium represents an important mechanism in the regulation of cardiovascular function. We examined the relationship between a common, functional polymorphism of the human sEH gene and coronary artery calcification (CAC) in young, largely asymptomatic African-American and non-Hispanic white subjects.

Methods and Results— Multiple logistic regression and Tobit regression models were used to assess the relationship between the sEH Arg287Gln polymorphism and presence and quantity of CAC. Models adjusting for race (except in race-specific analyses), age, sex, smoking, body mass index, systolic blood pressure, LDL cholesterol, and HDL cholesterol were estimated. Allele and genotype frequency distributions were not significantly different between the 2 ethnic groups (P=0.22; P=0.17, respectively). The Arg287Gln polymorphism of the sEH gene was a significant predictor of CAC status in African-American participants, either alone or after adjusting for other risk factors. African-American subjects with at least 1 copy of the Gln287 allele had a 2-fold greater risk of having CAC compared with those not carrying this allele (95% CI, 1.1 to 2.9; P=0.02). There was no relationship between Arg287Gln polymorphism and the probability of having CAC in white participants (OR, 0.8; 95% CI, 0.5 to 1.3; P=0.49). Inferences from multivariable Tobit regression were similar to those obtained in the logistic regression models, indicating that the Arg287Gln polymorphism was a significant independent predictor of both presence and quantity of CAC in African-American but not white subjects.

Conclusions— These data suggest an intriguing and possibly novel role for sEH in the pathogenesis of atherosclerosis, which deserves additional investigation.

Key Words: genetics • calcium • atherosclerosis

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