Interaction Between CYP4F2 rs2108622 and CPY4A11 rs9333025 Variants Is Significantly Correlated with Susceptibility to Ischemic Stroke and 20-Hydroxyeicosatetraenoic Acid Level.

Abstract

To investigate the association of four variants of two CYP ω-hydroxylase genes and 20-hydroxyeicosatetraenoic acid (HETE) levels with ischemic stroke (IS) and whether gene-gene interactions between these genes increase the risk of IS. Three hundred ninety-six patients with IS and 378 controls were genotyped for rs2269231, rs9333025, rs2108622, and rs3093135. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. The 20-HETE levels was measured in 218 IS patients and 126 controls. The frequency of the GG genotype of rs9333025 was significantly higher in IS patients than in controls (p < 0.001). The GMDR analysis showed a significant gene-gene interaction between rs9333025 and rs2108622 (p = 0.0116). This gene-gene interaction predicted a significantly higher risk of IS in individuals carrying the genotypes of rs9333025 GG and rs2108622 GG (odds ratio = 1.92, 95% confidence interval = 1.12-4.26, p = 0.007). The plasma levels of 20-HETE were significantly higher in IS patients than in controls, and IS patients carrying the genotype combination of rs9333025 GG and rs2108622 GG had higher 20-HETE levels than IS patients with other combinations of the two variants. CYP4A1l rs9333025 GG and CYP4F2 rs2108622 GG two-loci interaction significantly increases the risk for IS and an elevated 20-HETE level.