scholarly journals Endothelial Nitric Oxide Synthase Tagging Single Nucleotide Polymorphisms and Recovery From Aneurysmal Subarachnoid Hemorrhage

2009 ◽  
Vol 11 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Sheila Alexander ◽  
Samuel Poloyac ◽  
Leslie Hoffman ◽  
Matthew Gallek ◽  
Dianxu Ren ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Subarachnoid Hemorrhage ◽  
Single Nucleotide Polymorphisms ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Enos Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Poor Recovery ◽  
Recovery Profile ◽  
Endothelial Nitric Oxide

Aneurysmal subarachnoid hemorrhage (SAH) is a hemorrhagic stroke subtype with a poor recovery profile. Cerebral vasospasm (CV), a narrowing of the cerebral vasculature, significantly contributes to the poor recovery profile. Variation in the endothelial nitric oxide (NO) synthase (eNOS) gene has been implicated in CV and outcome after SAH. The purpose of this project was to explore the potential association between three eNOS tagging single nucleotide polymorphisms (SNPs) and recovery from SAH. We included 195 participants with a diagnosis of SAH and DNA and 6-month outcome data available but without preexisting neurologic disease/deficit. Genotyping was performed using an ABI Prism 7000 Sequence Detection System and TaqMan assays. CV was verified by cerebral angiogram independently read by a neurosurgeon on 118 participants. Modified Rankin Scores (MRS) and Glasgow Outcome Scale (GOS) scores were collected 6 months posthemorrhage. Data were analyzed using descriptive statistics, analysis of variance (ANOVA) and chi-square analysis as appropriate. The sample was primarily female (n = 147; 75.4%) and White (n = 178; 91.3%) with a mean age of 54.6 years. Of the participants with CV data, 56 (47.5%) developed CV within 14 days of SAH. None of the SNPs individually were associated with CV presence; however, a combination of the three variant SNPs was significantly associated with CV (p = .017). Only one SNP (rs1799983, variant allele) was associated with worse 6-month GOS scores (p < .001) and MRS (p < .001). These data indicate that the eNOS gene plays a role in the response to SAH, which may be explained by an influence on CV.

scholarly journals Endothelial Nitric Oxide Synthase Gene Single-Nucleotide Polymorphism Predicts Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

2008 ◽  
Vol 28 (6) ◽  
pp. 1204-1211 ◽  
Author(s):  
Robert M Starke ◽  
Grace H Kim ◽  
Ricardo J Komotar ◽  
Zachary L Hickman ◽  
Eric M Black ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Subarachnoid Hemorrhage ◽  
Nitric Oxide Synthase ◽  
Cerebral Vasospasm ◽  
Endothelial Nitric Oxide Synthase ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Enos Gene ◽  
Single Nucleotide ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.

Association between factor XIII single nucleotide polymorphisms and aneurysmal subarachnoid hemorrhage

2009 ◽  
Vol 110 (3) ◽  
pp. 475-481 ◽  
Author(s):  
Claes Ladenvall ◽  
Ludvig Csajbok ◽  
Karin Nylén ◽  
Katarina Jood ◽  
Bengt Nellgård ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Single Nucleotide Polymorphisms ◽  
Plasminogen Activator ◽  
Factor Xiii ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Tissue Type ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Pai 1

Object Family studies have suggested a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (aSAH), but the underlying genetic risk factors remain poorly defined. There is an activation of the fibrinolytic system in aSAH, and fibrinolytic markers may be useful in predicting outcome. The authors investigate associations between putative functional variants in genes of importance for fibrinolysis and aSAH and/or outcome following aSAH. Methods One hundred eighty-three patients presenting with aSAH at a neurointensive care unit were consecutively recruited. Two healthy controls per case, matched for age, sex, and geographic region, were randomly recruited. Outcome was assessed after 1 year according to the extended Glasgow Outcome Scale. Single nucleotide polymorphisms (SNPs) in the tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and factor XIII (FXIII) genes were investigated. Results Participants carrying the FXIII 34Leu allele showed an increased risk of aSAH. When adjusting for smoking and hypertension, 2 haplotypes, differing on either the FXIII Val34Leu or the Pro564Leu position, showed an association to aSAH. No significant association was observed for the tPA -7351 C > T, PAI-1 -675 4G > 5G, or TAFI Ala147Thr SNPs. No specific SNP or haplotype was associated with outcome after aSAH, whereas a weak association was observed for a tPA/PAI-1 genotype combination. Conclusions Polymorphisms in the FXIII gene showed association to aSAH. The finding of an increased risk of bleeding in FXIII 34Leu carriers is biologically plausible.

Single nucleotide polymorphisms in theNOS2andNOS3genes are associated with exhaled nitric oxide

2012 ◽  
Vol 49 (3) ◽  
pp. 200-205 ◽  
Author(s):  
Santosh Dahgam ◽  
Fredrik Nyberg ◽  
Lars Modig ◽  
Åsa Torinsson Naluai ◽  
Anna-Carin Olin
Keyword(s):  
Nitric Oxide ◽  
Single Nucleotide Polymorphisms ◽  
Exhaled Nitric Oxide ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Matrix metalloproteinase-9 gene polymorphisms and their interaction with environment on subarachnoid hemorrhage risk

2018 ◽  
Vol 243 (9) ◽  
pp. 749-753 ◽  
Author(s):  
Tao Wang ◽  
Wanxing Fu ◽  
Shuang Song ◽  
Yanlong Han ◽  
Lihong Yao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Single Nucleotide Polymorphisms ◽  
Matrix Metalloproteinase ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Matrix Metalloproteinase 9 ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hemorrhage Risk ◽  
Metalloproteinase 9

The current study aimed to investigate the relations of three single nucleotide polymorphisms of matrix metalloproteinase-9 gene, and single nucleotide polymorphisms-smoking interaction to subarachnoid hemorrhage risk. The optimal pattern of the interaction among single nucleotide polymorphisms and smoking was selected by generalized multifactor dimensionality reduction. The association between the three single nucleotide polymorphisms within the matrix metalloproteinase-9 gene was analyzed by logistic regression test. As well as genetic risk of subarachnoid hemorrhage interactions with smoking, the risk of subarachnoid hemorrhage in carriers with the rs3918242 (T) was significantly higher than in carriers carrying CC (genotype: CT + TT vs. CC), adjusted OR (95% CI) = 1.58 (1.25–2.03), and in carriers carrying rs17576- (genotype: AG + GG vs. AA), adjust OR (95% CI) = 1.62 (1.19–2.13). However, after adjusting for covariates, we did not find any direct association between rs17577 and subarachnoid hemorrhage risk. The generalized multifactor dimensionality reduction model shows a potential relation between rs3918242 and smoking risk for subarachnoid hemorrhage ( P = 0.0010). After covariates adjustment, current smokers with rs3918242-CT or TT genotype, compared to never-smokers with rs3918242-CC genotype, OR (95% CI) = 2.57 (1.74–3.46), have a higher subarachnoid hemorrhage risk. Our study showed that the rs3918242 (T) and rs17576 (G), the cross reaction between rs3918242 and smoking increased the risk of subarachnoid hemorrhage. Impact statement Matrix metalloproteinase-9 ( MMP-9) is a possible candidate gene for some diseases, including metabolic syndrome, stroke, coronary artery disease (CAD). But to date, limited data focused on the relationship between MMP-9 gene SNPs and SAH susceptibility. The purpose of this study was to evaluate SNPs of MMP-9 gene and their interaction with environmental factors with SAH risk based on a Chinese population.

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