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.

TitlePolymorphism 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.
Publication TypeJournal Article
Year of Publication2004
AuthorsFornage, M, Boerwinkle, E, Doris, PA, Jacobs, D, Liu, K, Wong, ND
JournalCirculation
Volume109
Issue3
Pagination335-9
Date Published2004 Jan 27
ISSN1524-4539
KeywordsAdolescent, Adult, African Americans, Calcinosis, Coronary Artery Disease, Coronary Vessels, Epoxide Hydrolases, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Male, Polymorphism, Genetic, Risk Factors
Abstract

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.

DOI10.1161/01.CIR.0000109487.46725.02
Alternate JournalCirculation
PubMed ID14732757
Grant ListN01-HC-48047 / HC / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
NS41466 / NS / NINDS NIH HHS / United States
R01-HL69126 / HL / NHLBI NIH HHS / United States