title: Interactions Among CYP2C8, EPHX2, and CYP4A11 Variants and CYP Plasma Metabolite Levels in Ischemic Stroke.
abstract: OBJECTIVE
  To better understand the relationship between the interactions among rs17110453, rs751141, and rs9333025 variants and plasma levels of cytochrome P450 (CYP) metabolites, i.e.,20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs) in ischemia stroke (IS).
  
  
  METHODS
  We measured plasma CYP metabolite levels in 218 acute IS cases and 126 controls, and a subset of samples were assessed to further understand the association between relevant variants and IS risk in our previous study. We assessed the associations between variant interactions and levels of 20-HETE, EETs, and DiHETEs as well as the associations between levels of 20-HETE, EETs, and DiHETEs and IS risk after adjusting for other potential confounders. Furthermore, the association between variant interactions and IS risk after adjusting for other covariates, including CYP metabolites levels, was evaluated.
  
  
  RESULTS
  The interactions among variants rs17110453, rs751141, and rs9333025 were significantly associated with high 20-HETE, high DiHETEs, and low EETs after adjusting for the status of diabetes mellitus and hypertension. High 20-HETE, high DiHETEs, and low EETs were independent risk factors for IS after adjusting for hypertension, diabetes mellitus, and the interactions among rs17110453, rs751141, and rs9333025. Furthermore, the interactions among rs17110453, rs751141, and rs9333025 were significantly associated with a higher risk of IS after adjusting for CYP metabolites (OR=2.02, 95% CI: 1.28-5.27, P=0.007).
  
  
  CONCLUSIONS
  The association between the interactions among rs17110453, rs751141, and rs9333025 and IS risk in Chinese population may be partly but not exclusively mediated by plasma levels of 20-HETE, EETs, and DHETs. Further well-designed studies are warranted to replicate this finding.
authors.affiliation: Department of Neurology, The People's Hospital of Deyang City.
authors.forename: Xingyang
authors.initials: X
authors.lastname: Yi
authors.forename: Lang
authors.initials: L
authors.lastname: Wu
authors.forename: Duanxiu
authors.initials: D
authors.lastname: Liao
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics*; D042926:Cytochrome P-450 CYP4A / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D008297:Male; D011379:Prognosis; D020521:Stroke / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D015415:Biomarkers; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C034922:5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human