{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:35:36Z","timestamp":1773300936203,"version":"3.50.1"},"reference-count":33,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Object<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u201319.91]) and death (OR 7.52 [95% CI 1.27\u201344.46]) in the K55R group, but no change in the odds of new stroke (OR 0.56 [95% CI 0.16\u20131.96]) or death (OR 3.09 [95% CI 0.51\u201318.52]) 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 \u2264 3 (OR 0.23 [95% CI 0.06\u20130.82]). There were no significant differences in the odds of neurological deterioration due to DCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Genetic polymorphisms of sEH are associated with neurological and vital outcomes after aneurysmal SAH.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2014.7.jns131990","type":"journal-article","created":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T17:54:58Z","timestamp":1411062898000},"page":"1359-1366","source":"Crossref","is-referenced-by-count":22,"title":["Genetic variation in soluble epoxide hydrolase: association with outcome after aneurysmal subarachnoid hemorrhage"],"prefix":"10.3171","volume":"121","author":[{"given":"Ross P.","family":"Martini","sequence":"first","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Ward","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic A.","family":"Siler","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie M.","family":"Eastman","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan W.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohan N.","family":"Borkar","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabil J.","family":"Alkayed","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology & Perioperative Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aclan","family":"Dogan","sequence":"additional","affiliation":[{"name":"Neurological Surgery, Oregon Health & Science University; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin S.","family":"Cetas","sequence":"additional","affiliation":[{"name":"Neurological Surgery, Oregon Health & Science University; and"},{"name":"Portland Veterans Affairs Medical Center, Portland, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-jns131990","series-title":"J Neurochem","first-page":"632","article-title":"Epoxyeicosatrienoic acids enhance axonal growth in primary sensory and cortical neuronal cell cultures","volume":"117","author":"Abdu","year":"2011"},{"key":"b2-jns131990","series-title":"Bioorg Med Chem Lett","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.bmcl.2010.12.042","article-title":"1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia","volume":"21","author":"Anandan","year":"2011"},{"key":"b3-jns131990","series-title":"Neurocrit Care","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s12028-011-9605-9","article-title":"Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference","volume":"15","author":"Diringer","year":"2011"},{"key":"b4-jns131990","series-title":"Acta Neurochir Suppl","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/978-3-7091-1192-5_26","article-title":"Spreading ischemia after aneurysmal subarachnoid hemorrhage","volume":"115","author":"Dreier","year":"2013"},{"key":"b5-jns131990","series-title":"Pharmacogenet Genomics","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1097\/FPC.0b013e3283349ec9","article-title":"Homozygosity for the EPHX2 K55R polymorphism increases the long-term risk of ischemic stroke in men: a study in Swedes","volume":"20","author":"Fava","year":"2010"},{"key":"b6-jns131990","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"15334","DOI":"10.1016\/S0021-9258(18)66872-3","article-title":"Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acids. Influence of stereochemistry","volume":"261","author":"Fitzpatrick","year":"1986"},{"key":"b7-jns131990","series-title":"Prostaglandins Other Lipid Mediat","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.prostaglandins.2006.05.003","article-title":"Epoxyeicosatrienoic acids, cell signaling and angiogenesis","volume":"82","author":"Fleming","year":"2007"},{"key":"b8-jns131990","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1093\/hmg\/ddi315","article-title":"The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke","volume":"14","author":"Fornage","year":"2005"},{"key":"b9-jns131990","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1161\/STROKEAHA.107.502179","article-title":"Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with an increased risk of ischemic stroke in white Europeans","volume":"39","author":"Gschwendtner","year":"2008"},{"key":"b10-jns131990","series-title":"Future Neurol","doi-asserted-by":"publisher","first-page":"179","DOI":"10.2217\/14796708.4.2.179","article-title":"Soluble epoxide hydrolase inhibition: targeting multiple mechanisms of ischemic brain injury with a single agent","volume":"4","author":"Iliff","year":"2009"},{"key":"b11-jns131990","series-title":"Am J Physiol Heart Circ Physiol","doi-asserted-by":"publisher","first-page":"H1352","DOI":"10.1152\/ajpheart.00950.2008","article-title":"Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels","volume":"296","author":"Iliff","year":"2009"},{"key":"b12-jns131990","series-title":"Cerebrovasc Dis","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1159\/000306645","article-title":"Association of platelet and leukocyte counts with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage","volume":"29","author":"Kasius","year":"2010"},{"key":"b13-jns131990","series-title":"Clin Neurol Neurosurg","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.clineuro.2012.09.006","article-title":"Clinical characteristics and outcomes of neurogenic stress cadiomyopathy in aneurysmal subarachnoid hemorrhage","volume":"115","author":"Kilbourn","year":"2013"},{"key":"b14-jns131990","series-title":"Trends Neurosci","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.tins.2008.11.005","article-title":"Astrocytes and the regulation of cerebral blood flow","volume":"32","author":"Koehler","year":"2009"},{"key":"b15-jns131990","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1523\/JNEUROSCI.0056-07.2007","article-title":"Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury","volume":"27","author":"Koerner","year":"2007"},{"key":"b16-jns131990","series-title":"Front Biosci","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.2741\/2889","article-title":"Soluble epoxide hydrolase: regulation by estrogen and role in the inflammatory response to cerebral ischemia","volume":"13","author":"Koerner","year":"2008"},{"key":"b17-jns131990","series-title":"JAMA","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1001\/jama.1993.03510240069035","article-title":"A new simplified acute physiology score (SAPS II) based on a European\/North American multicenter study","volume":"270","author":"Le Gall","year":"1993"},{"key":"b18-jns131990","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1093\/hmg\/ddl085","article-title":"Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study","volume":"15","author":"Lee","year":"2006"},{"key":"b19-jns131990","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1161\/hs1001.097108","article-title":"Transcranial Doppler versus angiography in patients with vasospasm due to a ruptured cerebral aneurysm: a systematic review","volume":"32","author":"Lysakowski","year":"2001"},{"key":"b20-jns131990","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1161\/01.STR.0000133132.76983.8e","article-title":"Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage","volume":"35","author":"Rabinstein","year":"2004"},{"key":"b21-jns131990","series-title":"J Neurol Neurosurg Psychiatry","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1136\/jnnp.2006.112730","article-title":"Non-infectious fever in the neurological intensive care unit: incidence, causes and predictors","volume":"78","author":"Rabinstein","year":"2007"},{"key":"b22-jns131990","series-title":"J Neurol Neurosurg Psychiatry","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1136\/jnnp.68.3.337","article-title":"Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands","volume":"68","author":"Roos","year":"2000"},{"key":"b23-jns131990","series-title":"Br J Anaesth","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/bja\/aes264","article-title":"Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm","volume":"109","author":"Rowland","year":"2012"},{"key":"b24-jns131990","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"28873","DOI":"10.1074\/jbc.M001153200","article-title":"Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms","volume":"275","author":"Sandberg","year":"2000"},{"key":"b25-jns131990","series-title":"Prog Lipid Res","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0163-7827(03)00049-3","article-title":"Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function","volume":"43","author":"Spector","year":"2004"},{"key":"b26-jns131990","series-title":"Arch Biochem Biophys","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.abb.2004.05.003","article-title":"Polymorphisms in human soluble epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure","volume":"427","author":"Srivastava","year":"2004"},{"key":"b27-jns131990","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1227\/01.NEU.0000065154.04824.9E","article-title":"Intraoperative detection of early microvasospasm in patients with subarachnoid hemorrhage by using orthogonal polarization spectral imaging","volume":"52","author":"Uhl","year":"2003"},{"key":"b28-jns131990","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1161\/STROKEAHA.110.597914","article-title":"Cerebral infarction after subarachnoid hemorrhage contributes to poor outcome by vasospasm-dependent and -independent effects","volume":"42","author":"Vergouwen","year":"2011"},{"key":"b29-jns131990","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1038\/jcbfm.2008.74","article-title":"Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia","volume":"28","author":"Vergouwen","year":"2008"},{"key":"b30-jns131990","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1161\/STROKEAHA.110.589275","article-title":"Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group","volume":"41","author":"Vergouwen","year":"2010"},{"key":"b31-jns131990","series-title":"Pharmacogenet Genomics","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1097\/FPC.0b013e3282f313e8","article-title":"Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population","volume":"18","author":"Zhang","year":"2008"},{"key":"b32-jns131990","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1038\/sj.jcbfm.9600494","article-title":"Soluble epoxide hydrolase: a novel therapeutic target in stroke","volume":"27","author":"Zhang","year":"2007"},{"key":"b33-jns131990","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1161\/STROKEAHA.107.508325","article-title":"Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia","volume":"39","author":"Zhang","year":"2008"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/121\/6\/article-p1359.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/121\/6\/article-p1359.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/121\/6\/article-p1359.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,16]],"date-time":"2023-07-16T17:01:37Z","timestamp":1689526897000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/121\/6\/article-p1359.xml"}},"subtitle":["Clinical article"],"short-title":[],"issued":{"date-parts":[[2014,12]]},"references-count":33,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2014.7.jns131990","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12]]}}}