1. ^*Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
2. ^†Department of Microarray Shared Resource, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
3. ^‡Department of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
4. ^§Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
5. ^¶Mayo Stroke Center, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

Correspondence: Irene Meissner, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA; E-mail: meissner.irene@mayo.edu.

Received 21 August 2003; Revised 5 October 2003; Accepted 17 November 2003.

Abstract

Rupture of an intracranial aneurysm (subarachnoid hemorrhage) is a potentially devastating condition frequently complicated by delayed cerebral ischemia from sustained contraction of intracranial arteries (cerebral vasospasm). There is mounting evidence linking the formation of intracranial aneurysms and the pathogenesis of post-subarachnoid hemorrhage vasospasm to aberrant bioavailability and action of the vasodilator molecule nitric oxide generated by isoforms of nitric oxide synthase. In humans, the gene encoding the endothelial isoform of nitric oxide synthase (eNOS) is known to be polymorphic, with certain polymorphisms associated with increased cardiovascular disease susceptibility. In this prospective clinical study involving 141 participants, we used gene microarray technology to demonstrate that the eNOS gene intron-4 27-base pair variable number tandem repeat polymorphism (eNOS 27 VNTR) predicts susceptibility to intracranial aneurysm rupture, while the eNOS gene promoter T-786C single nucleotide polymorphism (eNOS T-786C SNP) predicts susceptibility to post-subarachnoid hemorrhage vasospasm. We believe that genetic information such as this, which can be obtained expeditiously at the time of diagnosis, may be used as a helpful adjunct to other clinical information aimed at predicting and favorably modifying the clinical course of persons with intracranial aneurysms.