Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Robert M. Starke, Grace H. Kim, Ricardo J. Komotar, Zachary L. Hickman, Eric M. Black, Maritza B. Rosales, Christopher P. Kellner, David K. Hahn, Marc L. Otten, John Edwards, Tao Wang, James J. Russo, Stephan A. Mayer, Edward S. Connolly

Research output: Contribution to journalArticle

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Abstract

Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.

Original languageEnglish (US)
Pages (from-to)1204-1211
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume28
Issue number6
DOIs
StatePublished - Jun 30 2008

Fingerprint

Intracranial Vasospasm
Nitric Oxide Synthase Type III
Subarachnoid Hemorrhage
Single Nucleotide Polymorphism
Alleles
Odds Ratio
Genes
Spasm
Confidence Intervals
Genotype
Coronary Aneurysm
Logistic Models
Regression Analysis
Prospective Studies
Morbidity
Mortality
Incidence

Keywords

  • Endothelial nitric oxide synthase
  • Intracranial aneurysm
  • Nitric oxide
  • Polymorphism
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage. / Starke, Robert M.; Kim, Grace H.; Komotar, Ricardo J.; Hickman, Zachary L.; Black, Eric M.; Rosales, Maritza B.; Kellner, Christopher P.; Hahn, David K.; Otten, Marc L.; Edwards, John; Wang, Tao; Russo, James J.; Mayer, Stephan A.; Connolly, Edward S.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 28, No. 6, 30.06.2008, p. 1204-1211.

Research output: Contribution to journalArticle

Starke, RM, Kim, GH, Komotar, RJ, Hickman, ZL, Black, EM, Rosales, MB, Kellner, CP, Hahn, DK, Otten, ML, Edwards, J, Wang, T, Russo, JJ, Mayer, SA & Connolly, ES 2008, 'Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage', Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 6, pp. 1204-1211. https://doi.org/10.1038/jcbfm.2008.11
Starke, Robert M. ; Kim, Grace H. ; Komotar, Ricardo J. ; Hickman, Zachary L. ; Black, Eric M. ; Rosales, Maritza B. ; Kellner, Christopher P. ; Hahn, David K. ; Otten, Marc L. ; Edwards, John ; Wang, Tao ; Russo, James J. ; Mayer, Stephan A. ; Connolly, Edward S. / Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage. In: Journal of Cerebral Blood Flow and Metabolism. 2008 ; Vol. 28, No. 6. pp. 1204-1211.
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abstract = "Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95{\%} confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95{\%} CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95{\%} CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.",
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T1 - Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage

AU - Starke, Robert M.

AU - Kim, Grace H.

AU - Komotar, Ricardo J.

AU - Hickman, Zachary L.

AU - Black, Eric M.

AU - Rosales, Maritza B.

AU - Kellner, Christopher P.

AU - Hahn, David K.

AU - Otten, Marc L.

AU - Edwards, John

AU - Wang, Tao

AU - Russo, James J.

AU - Mayer, Stephan A.

AU - Connolly, Edward S.

PY - 2008/6/30

Y1 - 2008/6/30

N2 - Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.

AB - Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.

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KW - Intracranial aneurysm

KW - Nitric oxide

KW - Polymorphism

KW - Subarachnoid hemorrhage

KW - Vasospasm

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