Elsevier

Gene

Volume 512, Issue 1, 1 January 2013, Pages 35-40
Gene

Matrix metalloproteinase (MMP)-2 gene polymorphisms affect circulating MMP-2 levels in patients with migraine with aura

https://doi.org/10.1016/j.gene.2012.09.109Get rights and content
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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 1306T and C 735T) 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 735T 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.

Highlights

► Matrix metalloproteinases (MMP) are involved in migraine attacks. ► Genetic polymorphisms may affect MMP-2 levels in patients with migraine. ► We showed that the C 1306T and C 735T affect MMP-2 levels in patients with migraine. ► Patients with high MMP-2 levels may be exposed increased cardiovascular risk. ► Those patients may benefit from the use of MMP inhibitors.

Abbreviations

MMPs
Matrix metalloproteinases
BBB
Blood–brain barrier
TIMPs
Tissue inhibitor of MMPs
CSD
Cortical spreading depression
MWA
Migraine without aura
MA
Migraine with aura
RT-PCR
Real time-polymerase chain reaction
ELISA
Enzyme-linked immunosorbent assay

Keywords

Migraine
Matrix metalloproteinase-2
Polymorphisms
Haplotype
TIMP-2

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