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

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.

Region-specific disruption of the blood-brain barrier following repeated inflammatory dural stimulation in a rat model of chronic trigeminal allodynia

“…This sequence of activation could also sequester astrocytes from their vital role in neuronal modulation, changing neuronal excitability via microglial ATP release (45). Furthermore, mitochondrial dysfunction identified in migraineurs and this rat model could exacerbate changes in BBB permeability via the release of adenosine and reactive oxygen species (16,25,46,47). …”

“…Ictal and interictal serum levels of S100B, a marker for astrocyte activation, and MMP- 9, a matrix metalloproteinase that digests endothelial cell basal lamina and causes BBB breakdown, are increased in migraine patients (14,15). Two functional MMP-2 gene polymorphisms are also associated with migraine patients with aura (16). White matter brain lesions found in MRI images of migraine patients are proposed to be focal disruptions of the BBB (17,18).…”

Acupuncture Decreases Matrix Metalloproteinase-2 Activity in Patients with Migraine

“…It has been suggested that patients with increased MMP-2 levels could benefit from the use of MMP inhibitors. 13 Several data have demonstrated that cyclo-oxygenase inhibitors have a significant inhibitory effect on the activities of MMP-2 and MMP-9. 27 28 Cyclo-oxygenase inhibitors have an anti-inflammatory effect and are usually used in the treatment of migraine.…”

“…Studies have shown increases in favour of MMP in the MMP/TIMP ratio in Editor's choice Scan to access more free content migraine. 13 Studies have also shown that acupuncture reduces MMP expression in some inflammatory diseases, such as osteoarthritis. 14 This study investigated the effect of acupuncture therapy on levels and activation of MMP-2, a pathological increase in which has been shown to compromise the blood-brain barrier, in patients with migraine.…”

Can Functional Polymorphisms in <b><i>VEGF</i></b> and <b><i>MMP</i></b> Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

“…These include VEGF +936C/T, –1154A/G, –2578C/A, and –634G/C [18, 19], MMP2 –1306 C/T and –735 C/T, as well as MMP9 –1562 C/T [20, 21]. These potential genetic risk factors were analyzed in relation to known clinical risk factors of IVH.…”