title: Interaction Between CYP4F2 rs2108622 and CPY4A11 rs9333025 Variants Is Significantly Correlated with Susceptibility to Ischemic Stroke and 20-Hydroxyeicosatetraenoic Acid Level.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  CYP4A1l rs9333025 GG and CYP4F2 rs2108622 GG two-loci interaction significantly increases the risk for IS and an elevated 20-HETE level.
authors.affiliation: 1 Department of Neurology, People's Hospital of Deyang City , Deyang, China .
authors.forename: Duanxiu
authors.initials: D
authors.lastname: Liao
authors.affiliation: 1 Department of Neurology, People's Hospital of Deyang City , Deyang, China .
authors.forename: Xingyang
authors.initials: X
authors.lastname: Yi
authors.affiliation: 1 Department of Neurology, People's Hospital of Deyang City , Deyang, China .
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 2 Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College , Zhejiang, China .
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 2 Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College , Zhejiang, China .
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D042926:Cytochrome P-450 CYP4A / Q000235:genetics*; D000072470:Cytochrome P450 Family 4 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000097:blood / Q000235:genetics*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A