Endothelial Nitric Oxide Synthase Polymorphism Is Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

Philipp Hendrix, Paul M. Foreman, Mark R. Harrigan, Winfield S. Fisher, Nilesh A. Vyas, Robert H. Lipsky, Minkuan Lin, Beverly C. Walters, R. Shane Tubbs, Mohammadali Mohajel Shoja, Jean Francois Pittet, Mali Mathru, Christoph J. Griessenauer

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background and Purpose Nitric oxide is critical in the regulation of cerebral blood flow and smooth muscle proliferation. It is synthesized by 3 nitric oxide synthase (NOS) isoforms: neuronal, inducible, and endothelial NOS (eNOS). Aneurysmal subarachnoid hemorrhage (aSAH) causes endothelial dysfunction that, in turn, contributes to pathophysiologic processes surrounding aSAH. Previous studies reported an association of an eNOS single nucleotide polymorphism (SNP) with the clinical sequelae of aSAH. Here, we further elucidate the impact of this eNOS SNP on the clinical course after aSAH. Methods The Cerebral Aneurysm Renin Angiotensin System study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012–2015. Blood samples from all patients enrolled in the study were used for genetic evaluation using 5′exonuclease (Taqman) genotyping assays. Associations between the eNOS SNP rs2070744 (786 T->C) and clinical course after aSAH were analyzed. Results Samples from 149 aSAH patients were available for analysis. The C allele of the eNOS SNP independently predicted an increased risk for delayed cerebral ischemia (OR = 2.936, 95% CI 1.048–8.226, P = 0.040). The eNOS SNP rs2070744 was not associated with functional outcome or size of aneurysm at the time of rupture. Conclusions The present study is the first to demonstrate that the C allele of the eNOS SNP 786 T->C rs2070744 is independently associated with an increased risk for delayed cerebral ischemia following aSAH.

Original languageEnglish (US)
Pages (from-to)514-519
Number of pages6
JournalWorld Neurosurgery
Volume101
DOIs
StatePublished - May 1 2017
Externally publishedYes

Keywords

  • Aneurysm size
  • Delayed cerebral ischemia
  • Endothelial nitric oxide synthase
  • eNOS
  • eNOS SNP 786 T->C
  • Polymorphism
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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