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(Stroke. 2008;39:1103.)
© 2008 American Heart Association, Inc.

Original Contributions

Endothelial Nitric Oxide Synthase Polymorphism (–786TC) and Increased Risk of Angiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage

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

From the Departments of Neurology (N.U.K., P.R., M.R., W.S.S., W.L.Y.), Radiology (R.T.H.), Neurological Surgery (M.T.L., W.L.Y.), Anesthesia and Perioperative Care/Center for Cerebrovascular Research (H.K., L.P., W.L.Y.); and the Cardiovascular Research Institute (P.-Y.K.), University of California, San Francisco; Division of Research, Kaiser Permanente Medical Care Program (J.G.Z.), Oakland, Calif.

Correspondence to Nerissa U. Ko, MD, 505 Parnassus Ave, M830, San Francisco, CA 94143-0114. E-mail kon{at}ucsfmedctr.org

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 (–786TC SNP), and a coding SNP in exon 7 (894GT 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 –786TC 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 894GT 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 (–786TC) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.

Key Words: endothelial nitric oxide • genetics • subarachnoid hemorrhage • vasospasm

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