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

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• 作者：Flavia M. Gonç ; alves^a ; Alisson Martins-Oliveira^b ; Riccardo Lacchini^b ; Vanessa A. Belo^b ; Jose G. Speciali^c ; Fabí ; ola Dach^c ; Jose E. Tanus-Santos^b ; ^{tanus@fmrp.usp.br} ; ^{tanussantos@yahoo.com}
• 关键词：MMPs ; Matrix metalloproteinases ; BBB ; Blood&ndash ; 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 imm
• 刊名：Gene
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：512
• 期：1
• 页码：35-40
• 全文大小：331 K

文摘

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.