Background: CYP4A11 is a major cytochrome P450 in humans involved in the biosynthesis of 20-hydroxyeicosatetraenoic acids, products of arachidonic acid metabolism with important functions in the cardiovascular system. Several studies in Asian populations have been done to investigate associations between polymorphisms of the CYP4A11 gene and the risk of hypertension and coronary artery disease (CAD). The present study was designed to investigate association between common single nucleotide polymorphisms (SNP) rs3890011, rs9332978 and rs9333029 of CYP4A11 and the risk of CAD in Russian population.
Methods: DNA samples from 1,323 unrelated individuals comprising 637 patients with angiographically diagnosed CAD and 686 age- and sex-matched healthy subjects were genotyped for the polymorphisms using by the Mass-ARRAY 4 system.
Results: SNPs rs9332978 and rs3890011 were associated with the risk of CAD at a log-additive genetic model: odds ratios adjusted for sex, age and hypertension were 1.42 (95% CI: 1.14–1.78, P=0.002) and 1.21 (95% CI: 1.02–1.24, P=0.03), respectively. These SNPs were in a linkage disequilibrium (D’ =0.974, P<0.0001). Haplotype G-C-A (rs3890011, rs9332978 and rs9333029) of CYP4A11 showed a significant association with increased risk of CAD: odds ratio adjusted for sex, age and hypertension was 1.42 (95% CI: 1.13–1.79, P=0.003).
Conclusions: To our knowledge, this is the first study reporting association between SNP rs3890011 of CYP4A11 and the risk of CAD in Caucasians. Moreover, we found for the first time that polymorphism rs9332978 in the promoter of CYP4A11 could be a novel genetic marker of susceptibility to CAD. Further studies in independent races and ethnicities are required to confirm associations between polymorphisms of CYP4A11 and CAD and to assess whether the studied SNPs are informative markers in disease prediction for the purposes of personalized medicine.
