title: Multiple sclerosis: Association of gelatinase B/matrix metalloproteinase-9 with risk and clinical course the disease.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Valado
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Leitão
authors.affiliation: Portuguese Institute of Blood and Transplant, Rua Escola Inês de Castro, S. Martinho do Bispo, 3040-226 Coimbra, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Martinho
authors.affiliation: Laboratory of Neurochemistry, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Pascoal
authors.affiliation: School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Cerqueira
authors.affiliation: Department of Neurology, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Correia
authors.affiliation: 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.
authors.forename: Sónia
authors.initials: S
authors.lastname: Batista
authors.affiliation: 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.
authors.forename: Lívia
authors.initials: L
authors.lastname: Sousa
authors.affiliation: 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.
authors.forename: Inês
authors.initials: I
authors.lastname: Baldeiras
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D011379:Prognosis; D012737:Sex Factors; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D016899:Interferon-beta; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: IFN-beta therapy; MMP-9; Multiple sclerosis; Serum; −1562C/T polymorphism