Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage

Nerissa U. Ko, Pam Rajendran, Helen Kim, Martin Rutkowski, Ludmila Pawlikowska, Pui Yan Kwok, Randall T. Higashida, Michael T. Lawton, Wade S. Smith, Jonathan G. Zaroff, William L. Young

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND PURPOSE - Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients. METHODS - We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (-786T→C SNP), and a coding SNP in exon 7 (894G→T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography. RESULTS - For the eNOS promoter -786T→C SNP, the presence of the CC genotype compared with any T genotype (CT or TT) was associated with increased odds of vasospasm (odds ratio=2.97, 95% CI=1.32 to 6.67, P=0.008). No association with vasospasm was observed for the eNOS 894G→T or variable-number tandem-repeat polymorphisms. CONCLUSIONS - These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (-786T→C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.

Original languageEnglish (US)
Pages (from-to)1103-1108
Number of pages6
JournalStroke
Volume39
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Subarachnoid Hemorrhage
Nitric Oxide Synthase
Single Nucleotide Polymorphism
Cerebral Angiography
Minisatellite Repeats
Nitric Oxide
Genotype
Introns
Aneurysm
Rupture
Cause of Death
Exons
Cohort Studies
Logistic Models
Odds Ratio
Prospective Studies

Keywords

  • Endothelial nitric oxide
  • Genetics
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage. / Ko, Nerissa U.; Rajendran, Pam; Kim, Helen; Rutkowski, Martin; Pawlikowska, Ludmila; Kwok, Pui Yan; Higashida, Randall T.; Lawton, Michael T.; Smith, Wade S.; Zaroff, Jonathan G.; Young, William L.

In: Stroke, Vol. 39, No. 4, 01.04.2008, p. 1103-1108.

Research output: Contribution to journalArticle

Ko, NU, Rajendran, P, Kim, H, Rutkowski, M, Pawlikowska, L, Kwok, PY, Higashida, RT, Lawton, MT, Smith, WS, Zaroff, JG & Young, WL 2008, 'Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage', Stroke, vol. 39, no. 4, pp. 1103-1108. https://doi.org/10.1161/STROKEAHA.107.496596
Ko, Nerissa U. ; Rajendran, Pam ; Kim, Helen ; Rutkowski, Martin ; Pawlikowska, Ludmila ; Kwok, Pui Yan ; Higashida, Randall T. ; Lawton, Michael T. ; Smith, Wade S. ; Zaroff, Jonathan G. ; Young, William L. / Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage. In: Stroke. 2008 ; Vol. 39, No. 4. pp. 1103-1108.
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abstract = "BACKGROUND AND PURPOSE - Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients. METHODS - We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (-786T→C SNP), and a coding SNP in exon 7 (894G→T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography. RESULTS - For the eNOS promoter -786T→C SNP, the presence of the CC genotype compared with any T genotype (CT or TT) was associated with increased odds of vasospasm (odds ratio=2.97, 95{\%} CI=1.32 to 6.67, P=0.008). No association with vasospasm was observed for the eNOS 894G→T or variable-number tandem-repeat polymorphisms. CONCLUSIONS - These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (-786T→C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.",
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AU - Rajendran, Pam

AU - Kim, Helen

AU - Rutkowski, Martin

AU - Pawlikowska, Ludmila

AU - Kwok, Pui Yan

AU - Higashida, Randall T.

AU - Lawton, Michael T.

AU - Smith, Wade S.

AU - Zaroff, Jonathan G.

AU - Young, William L.

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N2 - BACKGROUND AND PURPOSE - Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients. METHODS - We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (-786T→C SNP), and a coding SNP in exon 7 (894G→T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography. RESULTS - For the eNOS promoter -786T→C SNP, the presence of the CC genotype compared with any T genotype (CT or TT) was associated with increased odds of vasospasm (odds ratio=2.97, 95% CI=1.32 to 6.67, P=0.008). No association with vasospasm was observed for the eNOS 894G→T or variable-number tandem-repeat polymorphisms. CONCLUSIONS - These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (-786T→C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.

AB - BACKGROUND AND PURPOSE - Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients. METHODS - We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (-786T→C SNP), and a coding SNP in exon 7 (894G→T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography. RESULTS - For the eNOS promoter -786T→C SNP, the presence of the CC genotype compared with any T genotype (CT or TT) was associated with increased odds of vasospasm (odds ratio=2.97, 95% CI=1.32 to 6.67, P=0.008). No association with vasospasm was observed for the eNOS 894G→T or variable-number tandem-repeat polymorphisms. CONCLUSIONS - These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (-786T→C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.

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