Matrix Metalloproteinase-9 Gene Polymorphism and Its Methylation in Stroke Patients

Background: Elevated matrix metalloproteinase-9 (MMP-9) following acute ischemic stroke is associated with blood-brain barrier breakdown and hemorrhagic conversion. Prior retrospective evidence suggests that sulfonylurea use may be associated with reduced risk of hemorrhagic conversion. We hypothesized that sulfonylureas may reduce MMP-9 level in stroke patients. Methods: Using serial plasma samples from six subjects in the Glyburide Advantage in Malignant Edema and Stroke Pilot trial (GAMES-Pilot), we evaluated the level of MMP-9 in human subjects presenting with large hemispheric stroke who were treated with intravenous glyburide (RP-1127). MMP-9 was measured in a control cohort with large ischemic stroke who were not treated with glyburide. Commercially available ELISA kits and gel zymography were used to measure MMP-9 at baseline and at approximately 48 hours after stroke. GAMES subjects had additional time points analyzed until approximately 84 hours after stroke. Results: Average MMP-9 level in glyburide-treated stroke patients was 47.2 ± 8.0 ng/mL compared to 143.4 ± 60.35 ng/mL in untreated control subjects (p=0.004). Zymography analysis demonstrated a significant decrease in the pro-enzyme but no change in the active form of MMP-9. There was no difference in the level of the MMP-9 specific inhibitor, TIMP-1. No subjects exhibited parenchymal hemorrhagic conversion on 24 hour head CT scan. Conclusions: Glyburide treatment in human stroke patients with large hemispheric stroke is associated reduced level of MMP-9. Elucidating the underlying mechanism of glyburide’s effect on MMP-9 and the risk of hemorrhagic conversion may highlight future directions of therapy, including in combination with intravenous tissue plasminogen activator (IV t-PA).

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Variants in matrix metalloproteinase‐9 gene are associated with hemorrhagic transformation in acute ischemic stroke patients with atherothrombosis, small artery disease, and cardioembolic stroke

Brain and Behavior ◽

10.1002/brb3.1294 ◽

2019 ◽

Vol 9 (6) ◽

Cited By ~ 5

Author(s):

Xingyang Yi ◽

Guo Sui ◽

Qiang Zhou ◽

Chun Wang ◽

Jing Lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Matrix Metalloproteinase ◽

Acute Ischemic Stroke ◽

Hemorrhagic Transformation ◽

Matrix Metalloproteinase 9 ◽

Cardioembolic Stroke ◽

Small Artery ◽

Stroke Patients ◽

Artery Disease ◽

Metalloproteinase 9

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Association between Increased Matrix Metalloproteinase-9 (MMP-9) Levels with Hyperglycaemia Incidence in Acute Ischemic Stroke Patients

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.459 ◽

2018 ◽

Vol 6 (11) ◽

pp. 2067-2072 ◽

Cited By ~ 2

Author(s):

Ismail Setyopranoto ◽

Rusdy Ghazali Malueka ◽

Andre Stefanus Panggabean ◽

I Putu Eka Widyadharma ◽

Ahmad Hamim Sadewa ◽

...

Keyword(s):

Ischemic Stroke ◽

Matrix Metalloproteinase ◽

Acute Ischemic Stroke ◽

Matrix Metalloproteinase 9 ◽

Blood Levels ◽

Stroke Patients ◽

Reference Hospital ◽

The Difference ◽

Increased Activity ◽

Metalloproteinase 9

BACKGROUND: Hyperglycemia is common in acute stroke patients. Hyperglycemia can induce the production of reactive oxygen species, causing increased activity of matrix metalloproteinase-9 (MMP-9). AIM: This study aimed to determine an association between the increased levels of MMP-9 and the incidence of hyperglycemia in acute ischemic stroke patients. METHODS: This is a case-control study. Acute ischemic stroke patients admitted to the Stroke Unit of a reference hospital in Yogyakarta, Indonesia was divided into the hyperglycemic and non-hyperglycemic group. Demographic and clinical characteristics of each subject were recorded, and blood levels of MMP-9 were measured. Seventy-one patients were recruited, 40 subjects in the hyperglycemic group and 31 subjects in the non-hyperglycemic group. RESULTS: The median levels of blood MMP-9 level in the hyperglycemic and non-hyperglycemic group were 974.37 and 748.48 ng/mL, respectively, and the difference was statistically not significant (95% CI, 191.24-2849.53; p = 0.07). When the calculated cut-off point of 600.99 ng/mL was used, the proportion of patients with higher MMP-9 levels was significantly more in the hyperglycemic group compared with the ones in the non-hyperglycemic group (82.5% and 54.8%, respectively; OR = 3.88; p = 0.011). CONCLUSION: We concluded that the proportion of patients with MMP-9 level >600.99 ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.

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Matrix metalloproteinase-9 promoter gene polymorphism (−1562C>T) in nasal polyposis

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2009.23.3371 ◽

2009 ◽

Vol 23 (6) ◽

pp. 568-570 ◽

Cited By ~ 13

Author(s):

Selim S. Erbek ◽

Erkan Yurtcu ◽

Seyra Erbek ◽

Feride I. Sahin

Keyword(s):

Gene Polymorphism ◽

Matrix Metalloproteinase ◽

Nasal Polyposis ◽

Matrix Metalloproteinase 9 ◽

Promoter Gene ◽

Metalloproteinase 9

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Matrix metalloproteinase-9 −1562 C/T gene polymorphism in Serbian patients with multiple sclerosis

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2007.06.022 ◽

2007 ◽

Vol 189 (1-2) ◽

pp. 147-150 ◽

Cited By ~ 12

Author(s):

M ZIVKOVIC ◽

T DJURIC ◽

E DINCIC ◽

R RAICEVIC ◽

D ALAVANTIC ◽

...

Keyword(s):

Multiple Sclerosis ◽

Gene Polymorphism ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Metalloproteinase 9

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Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy

The Egyptian Journal of Internal Medicine ◽

10.1186/s43162-021-00035-2 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

Kholoud Shalaby ◽

Rania Bahriz ◽

Nancy Mahsoub ◽

Mohammed M. El-Arman ◽

Ghada El-Said

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Gene Polymorphism ◽

Matrix Metalloproteinase ◽

Microvascular Complications ◽

Matrix Metalloproteinase 9 ◽

Metalloproteinase 9

Abstract Background Matrix metalloproteinase 9 (MMP-9) is an important inflammatory marker in diabetic nephropathy. Many studies assessed the association between MMP-9 gene polymorphism and different microvascular complications of type 2 diabetes mellitus, though the results were inconclusive and need further exploration. Our study aimed to assess the association between MMP-9 -1562C/T gene polymorphism and diabetic nephropathy in patients with type 2 diabetes mellitus. Results Taking CC genotype of rs3918242 (MMP-9-1562C/T SNP) as the reference genotype and C as the reference allele, TT genotype, T allele showed significantly lower frequency in diabetic nephropathy group than without nephropathy (2.9% versus 20%, 20% versus 35.7% respectively), with the possible significant protective effect against diabetic nephropathy development (OR = 0.269, 0.450 respectively); it was considered as an independent predictor for diabetic nephropathy occurrence. Conclusions This study suggested that T allele of MMP-9 -1562C/T single nucleotide polymorphism had a protective role against diabetic nephropathy development and also had a role for early prediction of patients susceptible to this complication, so it helps in prevention and management of those patients.

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