Epoxyeicosatrienoic Acids are Mediated by EPHX2 Variants and may be a Predictor of Early Neurological Deterioration in Acute Minor Ischemic Stroke

Aim: To investigatethe association of plasma epoxyeicosatrienoic acids (EETs) with early neurologic deterioration (END), and whether EETs are mediated by EPHX2 variants in patients with minor ischemic stroke (MIS). Method: This was a prospective, multi-center observational study in patients with acute MIS in the Chinese population. Plasma EETs levels were measured on admission. Single nucleotide polymorphisms (SNPs) of EPHX2rs751141 were genotyped using mass spectrometry. The primary outcome was END within 10 days after admission. END was defined as an increase in NIHSS of 2 or more points. The degree of disability was assessed using the modified Rankin Scale (mRS) at 3 months after admission. Results: A total of 322 patients were enrolled, of which 85 patients (26.4%) experienced END. The mean EETs level was 64.1 +/- 7.5 nmol/L. EETs levels were significantly lower in patients with END compared to patients without END. Frequency of EPHX2 rs751141 GG was higher in patients with END than in patients without END, and EPHX2 rs751141 GG genotype was associated with lower EETs levels. Low level (< 64.4 nmol/L) of EETs was an independent predictor of END (first and second quartiles) in multivariate analyses. END was associated with a higher risk of poor outcome (mRS scores 3-6) at 3 months. Conclusion: END is fairly common and associated with poor outcomes in acute MIS. EPHX2 variants may mediate EETs levels, and low levels of EETs may be a predictor for END in acute MIS.