Epoxyeicosatrienoic acids are related to early neurological deterioration and mediated by EPHX2 gene variants in acute minor ischemic stroke / 中华神经科杂志

ABSTRACT

Objective:To investigate the association of plasma epoxyeicosatrienoic acids (EETs) with early neurological deterioration (END), and whether EETs are mediated by EPHX2 gene variants in patients with minor ischemic stroke (MIS).Methods:This is a prospective, multi-center observational study in patients with acute MIS in the Chinese population. Acute MIS patients with the first onset and onset within 24 hours who were admitted to Deyang People′s Hospital, the Second Affiliated Hospital of Wenzhou Medical University and the Third Affiliated Hospital of Wenzhou Medical University from March 2013 to June 2015 were recruited. Plasma EETs levels were measured on admission. Single nucleotide polymorphisms of EPHX2 gene rs751141 were genotyped using mass spectrometry. The primary outcome was END within 10 days after admission. END was defined as an increase in National Institutes of Health Stroke Scale score of 2 or more points.Results:A total of 322 patients were enrolled, of which 85 (26.4%) patients experienced END. EETs levels were significantly lower in patients with END [(60.3±7.3) nmol/L] compared to patients without END [(68.4±8.1) nmol/L , t=8.464, P<0.001]. Frequency of EPHX2 gene rs751141 GG was higher in patients with END [66/85(77.6%)] than in patients without END [123/237(51.9%),χ2=17.130, P<0.001], and patients with EPHX2 gene rs751141 GG genotype showed lower EETs levels [GG (59.6±7.8) nmol/L, AG(67.9±8.2) nmol/L, AA(68.8±3.2) nmol/L, F=9.285, P<0.001]. Low level (≤64.3 nmol/L) of EETs was an independent predictor of END (31.5-51.3 nmol/L group OR=2.96,95% CI 1.18-8.77, P=0.02; 51.4-64.3 nmol/L group OR=2.46,95% CI 1.06-6.89, P=0.03) in multivariate analyses. END was associated with a higher risk of poor outcome (modified Rankin Scale scores 3-6) at 3 months ( OR=1.82,95% CI 1.46-2.35, P=0.02). Conclusion:END is fairly common and associated with poor outcomes in acute MIS. EPHX2 gene variants may mediate EETs levels, and low levels of EETs are related to END in acute MIS.