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

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.

► 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.