Endothelial nitric oxide synthase gene polymorphisms predict susceptibility to aneurysmal subarachnoid hemorrhage and cerebral vasospasm.
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.
Khurana
Vini G
VG
Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Sohni
Youvraj R
YR
Mangrum
Wells I
WI
McClelland
Robyn L
RL
O'Kane
Dennis J
DJ
Meyer
Fredric B
FB
Meissner
Irene
I
D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000235:genetics* / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000235:genetics* / Q000473:pathology
D007527:Isoenzymes; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III