Endothelial Nitric Oxide Synthase T-786C Single Nucleotide Polymorphism

A Putative Genetic Marker Differentiating Small Versus Large Ruptured Intracranial Aneurysms

Vini G. Khurana, Youvraj R. Sohni, Wells I. Mangrum, Robyn L. McClelland, Dennis J. O'Kane, Fredric B. Meyer, Irene Meissner

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background and Purpose - Anecdotal evidence exists for at least 2 subpopulations of intracranial saccular aneurysms, namely, those that may form rapidly and rupture when small versus those that enlarge slowly and may rupture particularly when ≥10 mm in diameter. We sought to determine whether the endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), implicated in cardiovascular disease susceptibility, could facilitate differentiation between small (≤5 mm) versus large (≥10 mm) ruptured aneurysms. Methods - In accordance with institutional guidelines, clinical data were recorded prospectively and genomic DNA was isolated from blood samples obtained from 52 aneurysmal subarachnoid hemorrhage (SAH) patients (cases) and 90 randomly selected controls. Samples were assayed for eNOS gene promoter T-786C SNP with the use of gene microarray technology. Statistical analyses included multiple logistic regression. Results - Although there was no difference in genotype distributions between cases and controls, all 13 patients with large aneurysms were (T/C) heterozygous for the polymorphism, while 9 of 22 patients (41%) with small aneurysms were (T/T or C/C) homozygous (P=0.01). The mean (±SD) ruptured aneurysm diameter among all heterozygotes (8.5±5.2 mm) was significantly greater than that for C/C (6.0±2.3 mm) or T/T (4.7±1.8 mm) homozygotes (P=0.04). With the use of multivariate analysis, heterozygosity remained significantly associated with aneurysm size ≥10 mm (P=0.03). Conclusions - The eNOS T-786C SNP distinguishes genetically between small and large ruptured aneurysms. Although not predictive of SAH in the population at large, our data suggest that among persons with known intracranial aneurysms, eNOS T-786C genotype may be a factor influencing the size at which an aneurysm ruptures, a finding that should be taken into consideration along with other anatomic features of the aneurysm.

Original languageEnglish (US)
Pages (from-to)2555-2559
Number of pages5
JournalStroke
Volume34
Issue number11
DOIs
StatePublished - Nov 2003

Fingerprint

Ruptured Aneurysm
Nitric Oxide Synthase Type III
Intracranial Aneurysm
Genetic Markers
Aneurysm
Single Nucleotide Polymorphism
Rupture
Subarachnoid Hemorrhage
Genotype
Disease Susceptibility
Homozygote
Heterozygote
Genes
Cardiovascular Diseases
Multivariate Analysis
Logistic Models
Guidelines
Technology
DNA
Population

Keywords

  • Aneurysm, ruptured
  • Genetics
  • Intracranial aneurysm
  • Nitric oxide synthase
  • Polymorphism
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Endothelial Nitric Oxide Synthase T-786C Single Nucleotide Polymorphism : A Putative Genetic Marker Differentiating Small Versus Large Ruptured Intracranial Aneurysms. / Khurana, Vini G.; Sohni, Youvraj R.; Mangrum, Wells I.; McClelland, Robyn L.; O'Kane, Dennis J.; Meyer, Fredric B.; Meissner, Irene.

In: Stroke, Vol. 34, No. 11, 11.2003, p. 2555-2559.

Research output: Contribution to journalArticle

Khurana, Vini G. ; Sohni, Youvraj R. ; Mangrum, Wells I. ; McClelland, Robyn L. ; O'Kane, Dennis J. ; Meyer, Fredric B. ; Meissner, Irene. / Endothelial Nitric Oxide Synthase T-786C Single Nucleotide Polymorphism : A Putative Genetic Marker Differentiating Small Versus Large Ruptured Intracranial Aneurysms. In: Stroke. 2003 ; Vol. 34, No. 11. pp. 2555-2559.
@article{1f37dc6fa22d4a92b04c8e8ed526221d,
title = "Endothelial Nitric Oxide Synthase T-786C Single Nucleotide Polymorphism: A Putative Genetic Marker Differentiating Small Versus Large Ruptured Intracranial Aneurysms",
abstract = "Background and Purpose - Anecdotal evidence exists for at least 2 subpopulations of intracranial saccular aneurysms, namely, those that may form rapidly and rupture when small versus those that enlarge slowly and may rupture particularly when ≥10 mm in diameter. We sought to determine whether the endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), implicated in cardiovascular disease susceptibility, could facilitate differentiation between small (≤5 mm) versus large (≥10 mm) ruptured aneurysms. Methods - In accordance with institutional guidelines, clinical data were recorded prospectively and genomic DNA was isolated from blood samples obtained from 52 aneurysmal subarachnoid hemorrhage (SAH) patients (cases) and 90 randomly selected controls. Samples were assayed for eNOS gene promoter T-786C SNP with the use of gene microarray technology. Statistical analyses included multiple logistic regression. Results - Although there was no difference in genotype distributions between cases and controls, all 13 patients with large aneurysms were (T/C) heterozygous for the polymorphism, while 9 of 22 patients (41{\%}) with small aneurysms were (T/T or C/C) homozygous (P=0.01). The mean (±SD) ruptured aneurysm diameter among all heterozygotes (8.5±5.2 mm) was significantly greater than that for C/C (6.0±2.3 mm) or T/T (4.7±1.8 mm) homozygotes (P=0.04). With the use of multivariate analysis, heterozygosity remained significantly associated with aneurysm size ≥10 mm (P=0.03). Conclusions - The eNOS T-786C SNP distinguishes genetically between small and large ruptured aneurysms. Although not predictive of SAH in the population at large, our data suggest that among persons with known intracranial aneurysms, eNOS T-786C genotype may be a factor influencing the size at which an aneurysm ruptures, a finding that should be taken into consideration along with other anatomic features of the aneurysm.",
keywords = "Aneurysm, ruptured, Genetics, Intracranial aneurysm, Nitric oxide synthase, Polymorphism, Subarachnoid hemorrhage",
author = "Khurana, {Vini G.} and Sohni, {Youvraj R.} and Mangrum, {Wells I.} and McClelland, {Robyn L.} and O'Kane, {Dennis J.} and Meyer, {Fredric B.} and Irene Meissner",
year = "2003",
month = "11",
doi = "10.1161/01.STR.0000096994.53810.59",
language = "English (US)",
volume = "34",
pages = "2555--2559",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Endothelial Nitric Oxide Synthase T-786C Single Nucleotide Polymorphism

T2 - A Putative Genetic Marker Differentiating Small Versus Large Ruptured Intracranial Aneurysms

AU - Khurana, Vini G.

AU - Sohni, Youvraj R.

AU - Mangrum, Wells I.

AU - McClelland, Robyn L.

AU - O'Kane, Dennis J.

AU - Meyer, Fredric B.

AU - Meissner, Irene

PY - 2003/11

Y1 - 2003/11

N2 - Background and Purpose - Anecdotal evidence exists for at least 2 subpopulations of intracranial saccular aneurysms, namely, those that may form rapidly and rupture when small versus those that enlarge slowly and may rupture particularly when ≥10 mm in diameter. We sought to determine whether the endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), implicated in cardiovascular disease susceptibility, could facilitate differentiation between small (≤5 mm) versus large (≥10 mm) ruptured aneurysms. Methods - In accordance with institutional guidelines, clinical data were recorded prospectively and genomic DNA was isolated from blood samples obtained from 52 aneurysmal subarachnoid hemorrhage (SAH) patients (cases) and 90 randomly selected controls. Samples were assayed for eNOS gene promoter T-786C SNP with the use of gene microarray technology. Statistical analyses included multiple logistic regression. Results - Although there was no difference in genotype distributions between cases and controls, all 13 patients with large aneurysms were (T/C) heterozygous for the polymorphism, while 9 of 22 patients (41%) with small aneurysms were (T/T or C/C) homozygous (P=0.01). The mean (±SD) ruptured aneurysm diameter among all heterozygotes (8.5±5.2 mm) was significantly greater than that for C/C (6.0±2.3 mm) or T/T (4.7±1.8 mm) homozygotes (P=0.04). With the use of multivariate analysis, heterozygosity remained significantly associated with aneurysm size ≥10 mm (P=0.03). Conclusions - The eNOS T-786C SNP distinguishes genetically between small and large ruptured aneurysms. Although not predictive of SAH in the population at large, our data suggest that among persons with known intracranial aneurysms, eNOS T-786C genotype may be a factor influencing the size at which an aneurysm ruptures, a finding that should be taken into consideration along with other anatomic features of the aneurysm.

AB - Background and Purpose - Anecdotal evidence exists for at least 2 subpopulations of intracranial saccular aneurysms, namely, those that may form rapidly and rupture when small versus those that enlarge slowly and may rupture particularly when ≥10 mm in diameter. We sought to determine whether the endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), implicated in cardiovascular disease susceptibility, could facilitate differentiation between small (≤5 mm) versus large (≥10 mm) ruptured aneurysms. Methods - In accordance with institutional guidelines, clinical data were recorded prospectively and genomic DNA was isolated from blood samples obtained from 52 aneurysmal subarachnoid hemorrhage (SAH) patients (cases) and 90 randomly selected controls. Samples were assayed for eNOS gene promoter T-786C SNP with the use of gene microarray technology. Statistical analyses included multiple logistic regression. Results - Although there was no difference in genotype distributions between cases and controls, all 13 patients with large aneurysms were (T/C) heterozygous for the polymorphism, while 9 of 22 patients (41%) with small aneurysms were (T/T or C/C) homozygous (P=0.01). The mean (±SD) ruptured aneurysm diameter among all heterozygotes (8.5±5.2 mm) was significantly greater than that for C/C (6.0±2.3 mm) or T/T (4.7±1.8 mm) homozygotes (P=0.04). With the use of multivariate analysis, heterozygosity remained significantly associated with aneurysm size ≥10 mm (P=0.03). Conclusions - The eNOS T-786C SNP distinguishes genetically between small and large ruptured aneurysms. Although not predictive of SAH in the population at large, our data suggest that among persons with known intracranial aneurysms, eNOS T-786C genotype may be a factor influencing the size at which an aneurysm ruptures, a finding that should be taken into consideration along with other anatomic features of the aneurysm.

KW - Aneurysm, ruptured

KW - Genetics

KW - Intracranial aneurysm

KW - Nitric oxide synthase

KW - Polymorphism

KW - Subarachnoid hemorrhage

UR - http://www.scopus.com/inward/record.url?scp=0242525539&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242525539&partnerID=8YFLogxK

U2 - 10.1161/01.STR.0000096994.53810.59

DO - 10.1161/01.STR.0000096994.53810.59

M3 - Article

VL - 34

SP - 2555

EP - 2559

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 11

ER -