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Genetic variation in EPHX2 was significantly associated with risk of incident CHD in Caucasians, implicating EPHX2 as a potential cardiovascular disease-susceptibility gene. Single nucleotide polymorphisms (SNPs) in the human EPHX2 gene had been implicated in susceptibility to cardiovascular disease, including stroke. The human EPHX2 mutations may in part explain the genetic variability in sensitivity to ischemic brain injury and stroke outcome. Epoxide hydrolase is involved in metabolism of vasoactive and anti-inflammatory epoxyeicosatrienoic acids to their corresponding diols. Consequently, epoxide hydrolase 2 (EPHX2) is a candidate cardiovascular disease (CVD) gene. Genetic variation in EPHX2 is associated with forearm vasodilator responses in a bradykinin receptor- and endothelium-independent manner, suggesting an important role for soluble epoxide hydrolase in the regulation of vascular function in humans. EPHX2 variants may mediate EETs levels, and low levels of EETs may be a predictor for END in acute MIS.