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Objective: CYP4A11 and CYP4F2 are responsible for metabolizing arachidonic acid (AA) into 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor.The aim of the present study was to evaluate the associations between 4 single-nucleotide polymorphisms (SNPs) from thetwo genes and ischemic stroke, and whether these variants associations with atherothrombotic events after stroke.Methods: 396 patients with ischemic stroke and 378 controls were genotyped for 4 SNPs of the CYP4A11 gene (rs2269231, rs9333025) and CYP4F2 gene (rs2108622 ,rs3093135) using the matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS) methods.All patients were followed up 12-months for atherothrombotic events.Results: The frequency of GG genotype of rs9333025 was significantly higher in ischemic stroke patients than in controls (75.5% vs.65.6%, P<0.001).Multiple logistic regression analysis shows that rs9333025 GG was associated with significantly higher risk of ischemic stroke (adjusted for age, hypertension, diabetes; OR =1.82, 95% CI 1.24-5.04, P=0.016).The rs9333025 GG was associated with significantly higher atherothrombotic events than rs9333025 AG during 12 months after stroke (P=0.04).Multiple Cox regression analysis revealed that the rs9333025 GG was an independent risk factor for atherothrombotic events after adjustment for confounding factors (RR=1.87, 95% CI: 1.16-5.36, P =0.003).Conclusion: rs9333025 GG genotype increases susceptibility to ischemic stroke, and is associated with high frequencies of atherothrombotic events in stroke patients.