Genetic variation in soluble epoxide hydrolase: association with outcome after aneurysmal subarachnoid hemorrhage

Clinical article

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Object

Patients with aneurysmal subarachnoid hemorrhage (SAH) are at high risk for delayed cerebral ischemia (DCI) and stroke. Epoxyeicosatrienoic acids (EETs) play an important role in cerebral blood flow regulation and neuroprotection after brain injury. Polymorphisms in the gene for the enzyme soluble epoxide hydrolase (sEH), which inactivates EETs, are associated with ischemic stroke risk and neuronal survival after ischemia. This prospective observational study of patients with SAH compares vital and neurologic outcomes based on functional polymorphisms of sEH.

Methods

Allelic discrimination based on quantitative real-time polymerase chain reaction was used to differentiate wild-type sEH from K55R heterozygotes (predictive of increased sEH activity and reduced EETs) and R287Q heterozygotes (predictive of decreased sEH activity and increased EETs). The primary outcome was new stroke after SAH. Secondary outcomes were death, Glasgow Outcome Scale score, and neurological deterioration attributable to DCI.

Results

Multivariable logistic regression models adjusted for age at admission and Glasgow Coma Scale scores revealed an increase in the odds of new stroke (OR 5.48 [95% CI 1.51–19.91]) and death (OR 7.52 [95% CI 1.27–44.46]) in the K55R group, but no change in the odds of new stroke (OR 0.56 [95% CI 0.16–1.96]) or death (OR 3.09 [95% CI 0.51–18.52]) in patients with R287Q genotype, compared with wild-type sEH. The R287Q genotype was associated with reduced odds of having a Glasgow Outcome Scale score of ≤ 3 (OR 0.23 [95% CI 0.06–0.82]). There were no significant differences in the odds of neurological deterioration due to DCI.

Conclusions

Genetic polymorphisms of sEH are associated with neurological and vital outcomes after aneurysmal SAH.

Abbreviations used in this paper:ARDS = acute respiratory distress syndrome; CBF = cerebral blood flow; CSW = cerebral salt wasting; DCI = delayed cerebral ischemia; EET = epoxyeicosatrienoic acid; EVD = extraventricular drain; GCS = Glasgow Coma Scale; GOS = Glasgow Outcome Scale; ICU = intensive care unit; IQR = interquartile range; qPCR = quantitative polymerase chain reaction; SAH = subarachnoid hemorrhage; SAPS II = Simplified Acute Physiology Score; sEH = soluble epoxide hydrolase; SIADH = syndrome of inappropriate secretion of antidiuretic hormone; TCD = transcranial Doppler; WBC = white blood cell; WT = wild type.

Article Information

Address correspondence to: Justin S. Cetas, M.D., Ph.D., Department of Neurological Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239. email: cetasj@ohsu.edu.

Please include this information when citing this paper: published online September 12, 2014; DOI: 10.3171/2014.7.JNS131990.

© AANS, except where prohibited by US copyright law.

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