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Updated: May 17, 2026

Detection of Functional Matrix Metalloproteinases by Zymography
Published on: November 8, 2010
Matrix metalloproteinase (MMP)-2 gene polymorphisms affect circulating MMP-2 levels in patients with migraine with
Flavia M Gonçalves1, Alisson Martins-Oliveira, Riccardo Lacchini
1Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil.
Abstract:
Matrix metalloproteinases (MMP) are involved in the disruption of blood-brain barrier (BBB) during migraine attacks. In the present study, we hypothesized that two functional polymorphisms (C(-1306)T and C(-735)T) in MMP-2 gene and MMP-2 haplotypes are associated with migraine and modify MMP-2 and tissue inhibitor of MMP (TIMP)-2 levels in migraine. Genotypes for MMP-2 polymorphisms were determined by real time-PCR using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by gelatin zymography and ELISA, respectively, in 148 healthy women without history of migraine and in 204 women with migraine (153 without aura; MWA, and 51 with aura; MA). Patients with MA had higher plasma MMP-2 concentrations and MMP-2/TIMP-2 ratios than patients with MWA and controls (P<0.05). While MMP-2 genotype and haplotype distributions for the polymorphisms were similar among the groups (P>0.05), we found that the CC genotype for C(-735)T polymorphism and the CC haplotype were associated with higher plasma MMP-2 concentrations in MA group (P<0.05). Our findings may help to understand the role of MMP-2 and its genetic variants in the pathophysiology of migraine and to identify a particular group of migraine patients with increased MMP-2 levels that would benefit from the use of MMP inhibitors.
Insights
Matrix metalloproteinases (MMP) influence blood-brain barrier disruption in migraine. Specific MMP-2 gene variants (C(-735)T) and haplotypes are linked to elevated MMP-2 levels in migraine with aura patients.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Matrix metalloproteinases (MMP) play a role in blood-brain barrier (BBB) disruption during migraine.
- Understanding the genetic factors influencing MMP activity is crucial for migraine pathophysiology.
Purpose of the Study:
- To investigate the association between MMP-2 gene polymorphisms and haplotypes with migraine.
- To determine if these genetic variants modify MMP-2 and TIMP-2 levels in migraine patients.
Main Methods:
- Genotyping of MMP-2 polymorphisms (C(-1306)T and C(-735)T) using real-time PCR.
- Haplotype inference using the PHASE program.
- Quantification of plasma MMP-2 and TIMP-2 levels via gelatin zymography and ELISA in controls and migraineurs (with and without aura).
Main Results:
- Migraine with aura (MA) patients exhibited higher plasma MMP-2 concentrations and MMP-2/TIMP-2 ratios compared to migraine without aura (MWA) and control groups.
- No significant differences in MMP-2 genotype or haplotype distributions were observed among the groups.
- The CC genotype for the C(-735)T polymorphism and the CC haplotype were associated with increased plasma MMP-2 levels specifically in the MA group.
Conclusions:
- Genetic variants in the MMP-2 gene, particularly the C(-735)T polymorphism and CC haplotype, are associated with elevated MMP-2 levels in migraine with aura.
- These findings contribute to understanding MMP-2's role in migraine pathophysiology.
- Identifying migraine patients with increased MMP-2 levels may guide the use of MMP inhibitors for targeted therapy.
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