Ana Valado1, Maria João Leitão2, António Martinho3, Rui Pascoal4, João Cerqueira5, Inês Correia6, Sónia Batista7, Lívia Sousa7, Inês Baldeiras8. 1. Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Ciências Biomédicas Laboratoriais, Rua 5 de Outubro, S. Martinho do Bispo, Ap 7006, 3046-854 Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal. Electronic address: valado@estescoimbra.pt. 2. CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal. 3. Portuguese Institute of Blood and Transplant, Rua Escola Inês de Castro, S. Martinho do Bispo, 3040-226 Coimbra, Portugal. 4. Laboratory of Neurochemistry, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal. 5. School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. 6. Department of Neurology, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal. 7. Department of Neurology, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal. 8. CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal; Laboratory of Neurochemistry, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal.
Abstract
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and axonal degeneration of the central nervous system and a leading cause of disability in young adults. The matrix metalloproteinases in general and specially gelatinase B/metalloproteinase-9 (MMP-9) plays a role in the pathogenesis of multiple sclerosis. OBJECTIVE: To investigate the presence of the MMP-9 -1562C/T polymorphism in a Portuguese population of MS patients and assess its impact in susceptibility and course of the disease. The relation of MMP-9 serum levels with the polymorphism and with clinical and therapeutic factors will also be assessed. METHODS: Our study included 355 Caucasian individuals distributed as MS patients (n=169) and controls (n=186). Samples were genotyped for -1562C/T polymorphism by PCR-RFLP analysis. MMP-9 concentration in serum was analyzed using a commercially available enzyme-linked immunosorbent assay. RESULTS: A significant increase in T-allele frequency was found in female MS patients, but not in the total patient population. No association between the presence of the polymorphism and disease progression was found. MMP-9 serum concentrations were increased in patients, and although not influenced by the -1562C/T polymorphism, were modified by INF-beta therapy. CONCLUSION: Although we did not find an association of this polymorphism with disease susceptibility or prognosis, MMP-9 appears to be a good therapeutic response marker for multiple sclerosis.
BACKGROUND:Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and axonal degeneration of the central nervous system and a leading cause of disability in young adults. The matrix metalloproteinases in general and specially gelatinase B/metalloproteinase-9 (MMP-9) plays a role in the pathogenesis of multiple sclerosis. OBJECTIVE: To investigate the presence of the MMP-9-1562C/T polymorphism in a Portuguese population of MSpatients and assess its impact in susceptibility and course of the disease. The relation of MMP-9 serum levels with the polymorphism and with clinical and therapeutic factors will also be assessed. METHODS: Our study included 355 Caucasian individuals distributed as MSpatients (n=169) and controls (n=186). Samples were genotyped for -1562C/T polymorphism by PCR-RFLP analysis. MMP-9 concentration in serum was analyzed using a commercially available enzyme-linked immunosorbent assay. RESULTS: A significant increase in T-allele frequency was found in female MSpatients, but not in the total patient population. No association between the presence of the polymorphism and disease progression was found. MMP-9 serum concentrations were increased in patients, and although not influenced by the -1562C/T polymorphism, were modified by INF-beta therapy. CONCLUSION: Although we did not find an association of this polymorphism with disease susceptibility or prognosis, MMP-9 appears to be a good therapeutic response marker for multiple sclerosis.
Authors: Alessandra Aldinucci; Elena Bonechi; Tiziana Biagioli; Anna M Repice; Mario M D'Elios; Lorenzo Emmi; Giacomo Emmi; Elena Silvestri; Alessandro Barilaro; Clara Ballerini Journal: Ann Clin Transl Neurol Date: 2018-03-10 Impact factor: 4.511