Multiple sclerosis: Association of gelatinase B/matrix metalloproteinase-9 with risk and clinical course the disease

Mult Scler Relat Disord. 2017 Jan:11:71-76. doi: 10.1016/j.msard.2016.12.003. Epub 2016 Dec 13.

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.

Keywords: IFN-beta therapy; MMP-9; Multiple sclerosis; Serum; −1562C/T polymorphism.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Humans
  • Immunologic Factors / therapeutic use
  • Interferon-beta / therapeutic use
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Matrix Metalloproteinase 9 / genetics*
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / genetics*
  • Polymorphism, Single Nucleotide*
  • Portugal
  • Prognosis
  • Sex Factors
  • Treatment Outcome
  • White People / genetics
  • Young Adult

Substances

  • Biomarkers
  • Immunologic Factors
  • Interferon-beta
  • MMP9 protein, human
  • Matrix Metalloproteinase 9