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

Ross P. Martini, Jonathan Ward, Dominic A. Siler, Jamie M. Eastman, Jonathan W. Nelson, Rohan N. Borkar, Nabil Alkayed, Aclan Dogan, Justin Cetas

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

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.

Original languageEnglish (US)
Pages (from-to)1359-1366
Number of pages8
JournalJournal of Neurosurgery
Volume121
Issue number6
DOIs
StatePublished - Dec 1 2014

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Epoxide Hydrolases
Subarachnoid Hemorrhage
Stroke
Brain Ischemia
Glasgow Outcome Scale
Heterozygote
Cerebrovascular Circulation
Logistic Models
Genotype
Glasgow Coma Scale
Genetic Polymorphisms
Brain Injuries
Nervous System
Observational Studies
Real-Time Polymerase Chain Reaction
Ischemia
Prospective Studies
Acids
Enzymes

Keywords

  • ARDS = acute respiratory distress syndrome
  • CBF = cerebral blood flow
  • CSW = cerebral salt wasting
  • DCI = delayed cerebral ischemia
  • EET = epoxyeicosatrienoic acid
  • epoxyeicosatrienoic acids
  • 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
  • soluble epoxide hydrolase
  • subarachnoid hemorrhage
  • TCD = transcranial Doppler
  • vascular disorders
  • WBC = white blood cell
  • WT = wild type

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Genetic variation in soluble epoxide hydrolase : association with outcome after aneurysmal subarachnoid hemorrhage. / Martini, Ross P.; Ward, Jonathan; Siler, Dominic A.; Eastman, Jamie M.; Nelson, Jonathan W.; Borkar, Rohan N.; Alkayed, Nabil; Dogan, Aclan; Cetas, Justin.

In: Journal of Neurosurgery, Vol. 121, No. 6, 01.12.2014, p. 1359-1366.

Research output: Contribution to journalArticle

Martini, Ross P. ; Ward, Jonathan ; Siler, Dominic A. ; Eastman, Jamie M. ; Nelson, Jonathan W. ; Borkar, Rohan N. ; Alkayed, Nabil ; Dogan, Aclan ; Cetas, Justin. / Genetic variation in soluble epoxide hydrolase : association with outcome after aneurysmal subarachnoid hemorrhage. In: Journal of Neurosurgery. 2014 ; Vol. 121, No. 6. pp. 1359-1366.
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abstract = "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.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.",
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T1 - Genetic variation in soluble epoxide hydrolase

T2 - association with outcome after aneurysmal subarachnoid hemorrhage

AU - Martini, Ross P.

AU - Ward, Jonathan

AU - Siler, Dominic A.

AU - Eastman, Jamie M.

AU - Nelson, Jonathan W.

AU - Borkar, Rohan N.

AU - Alkayed, Nabil

AU - Dogan, Aclan

AU - Cetas, Justin

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.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.

AB - 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.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.

KW - ARDS = acute respiratory distress syndrome

KW - CBF = cerebral blood flow

KW - CSW = cerebral salt wasting

KW - DCI = delayed cerebral ischemia

KW - EET = epoxyeicosatrienoic acid

KW - epoxyeicosatrienoic acids

KW - EVD = extraventricular drain

KW - GCS = Glasgow Coma Scale

KW - GOS = Glasgow Outcome Scale

KW - ICU = intensive care unit

KW - IQR = interquartile range

KW - qPCR = quantitative polymerase chain reaction

KW - SAH = subarachnoid hemorrhage

KW - SAPS II = Simplified Acute Physiology Score

KW - sEH = soluble epoxide hydrolase

KW - SIADH = syndrome of inappropriate secretion of antidiuretic hormone

KW - soluble epoxide hydrolase

KW - subarachnoid hemorrhage

KW - TCD = transcranial Doppler

KW - vascular disorders

KW - WBC = white blood cell

KW - WT = wild type

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