title: 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.
authors.affiliation: Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Flavia M
authors.initials: FM
authors.lastname: Gonçalves
authors.forename: Alisson
authors.initials: A
authors.lastname: Martins-Oliveira
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lacchini
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Belo
authors.forename: Jose G
authors.initials: JG
authors.lastname: Speciali
authors.forename: Fabíola
authors.initials: F
authors.lastname: Dach
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D004827:Epilepsy / Q000150:complications; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020325:Migraine with Aura / Q000097:blood* / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D020778:Matrix Metalloproteinase 2