A Novel Polymorphism in the Promoter of theCYP4A11Gene Is Associated with Susceptibility to Coronary Artery Disease

Abstract

Enzymes CYP4A11 and CYP4F2 are involved in biosynthesis of vasoactive 20-hydroxyeicosatetraenoic acid and may contribute to pathogenesis of coronary artery disease (CAD). We investigated whether polymorphisms of theCYP4A11andCYP4F2genes are associated with the risk of CAD in Russian population. DNA samples from 1323 unrelated subjects (637 angiographically confirmed CAD patients and 686 age- and sex-matched healthy individuals) were genotyped for polymorphisms rs3890011, rs9332978, and rs9333029 ofCYP4A11and rs3093098 and rs1558139 ofCYP4F2by using the Mass-ARRAY 4 system. SNPs rs3890011 and rs9332978 ofCYP4A11were associated with increased risk of CAD in women: OR = 1.26, 95% CI: 1.02–1.57,P=0.004, andQ=0.01and OR = 1.45, 95% CI: 1.13–1.87,P=0.004, andQ=0.01, respectively. Haplotype G-C-A ofCYP4A11was associated with increased risk of CAD (adjusted OR = 1.41, 95% CI: 1.12–1.78, andP=0.0036). Epistatic interactions were found between rs9332978 ofCYP4A11and rs1558139 ofCYP4F2(Pinteraction=0.025). In silico analysis allowed identifying that SNP rs9332978 is located at a binding site for multiple transcription factors; many of them are known to regulate the pathways involved in the pathogenesis of CAD. This is the first study in Europeans that reported association between polymorphism rs9332978 ofCYP4A11and susceptibility to coronary artery disease.