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.

Gene
|October 10, 2012
PubMed

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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