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 1562 C/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 1562 C/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 1562 C/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.