Document Detail


Endothelial nitric oxide synthase gene polymorphisms predict susceptibility to aneurysmal subarachnoid hemorrhage and cerebral vasospasm.
MedLine Citation:
PMID:  15091109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Vini G Khurana; Youvraj R Sohni; Wells I Mangrum; Robyn L McClelland; Dennis J O'Kane; Fredric B Meyer; Irene Meissner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  24     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-04-19     Completed Date:  2004-05-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  291-7     Citation Subset:  IM    
Affiliation:
Department of Neurologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Female
Genetic Predisposition to Disease
Humans
Isoenzymes / genetics,  metabolism
Middle Aged
Nitric Oxide Synthase / genetics*,  metabolism
Nitric Oxide Synthase Type III
Oligonucleotide Array Sequence Analysis
Polymorphism, Genetic*
Promoter Regions, Genetic / genetics
Prospective Studies
Subarachnoid Hemorrhage / genetics*,  pathology
Vasospasm, Intracranial / genetics*,  pathology
Chemical
Reg. No./Substance:
0/Isoenzymes; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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