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.

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.

379 Matrix Metalloproteinase-9: A Key Contributor to Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 290-290
Author(s):  
Ananth K Vellimana ◽  
Meng-Liang Zhou ◽  
Itender Singh ◽  
Diane J Aum ◽  
James Nelson ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Matrix Metalloproteinase ◽  
Delayed Cerebral Ischemia ◽  
Experimental Models ◽  
Matrix Metalloproteinase 9 ◽  
Multiple Components ◽  
Neurobehavioral Deficits ◽  
Metalloproteinase 9 ◽  
Expression And Activity

Abstract INTRODUCTION Delayed cerebral ischemia (DCI) is an independent risk factor for poor outcome after subarachnoid hemorrhage (SAH) and is multi-factorial in etiology. A few prior studies have suggested a key role for matrix metalloproteinase-9 (MMP-9) in the pathogenesis of early brain injury (EBI) after SAH. In contrast, the role of MMP-9 in DCI is poorly understood. In this study, we examined the contribution of MMP-9 to DCI after SAH. METHODS Wild type (WT) and MMP-9-/− mice were subjected to sham or endovascular perforation SAH surgery. Daily neurobehavioral assessments were performed, and vasospasm was assessed on post-SAH Day 3. MMP-9 expression and activity were also assessed. In separate experiments, WT mice or MMP-9-/− were administrated vehicle or Minocycline and subjected to vasospasm, neurobehavioral, and microthrombi assessments. In another experiment, male New Zealand White rabbits were subjected to sham surgery or cisterna magna injection SAH, and administered vehicle or Minocycline, followed by vasospasm assessment on post-SAH day 3. RESULTS >SAH resulted in a significant increase in MMP-9 expression and activity. Genetic inhibition of MMP-9 (MMP-9-/− mice) and pharmacological inhibition of MMP-9 (pre-SAH Minocycline administration) resulted in significantly decreased vasospasm and neurobehavioral deficits after SAH. Post-SAH administration of Minocycline resulted in significant attenuation of multiple components of DCI including vasospasm, microthrombosis and neurobehavioral deficits. Consistent with experiments in mice both pre- and post-SAH administration of Minocycline attenuated vasospasm in rabbits. CONCLUSION Our study provides definitive mechanistic evidence that MMP-9 is a key player in the pathogenesis of DCI after SAH. We observed consistent attenuation of SAH-induced neurovascular deficits with both pre- and post-SAH administration of minocycline across different species and experimental models of SAH, and against multiple components of DCI. The excellent safety profile of minocycline in humans and promising results in experimental SAH studies suggest that a clinical trial in SAH patients is warranted.

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