An Association between Matrix Metalloproteinase-2 and TIMP-2 +853G/A Gene Polymorphisms and Multiple Sclerosis

Authors: Y. Benešová 1;  A. Vašků 2;  P. Štouračihash2 1,3 1,3
Authors‘ workplace: Neurologická klinika LF MU a FN Brno 1;  Ústav patologické fyziologie, LF MU, Brno 2;  CEITEC – Středoevropský techno­logický institut, MU, Brno 3
Published in: Cesk Slov Neurol N 2012; 75/108(3): 314-319
Category: Original Paper


Matrix metalloproteinases (MMPs) play an important role in the immunopathogenesis of multiple sclerosis (MS). They are notable contributors to the progression of inflammatory process, blood-brain barrier disruption, formation of MS lesions and demyelination. The matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) are the most important. They are expressed by T-lymphocytes and monocytes, the predominant group of inflammatory cells in active demyelinating plaques. In our previous study, we demonstrated a borderline association of MMP-2-1575G/A gene polymorphism with MS susceptibility. To date, no other genetic association study involving MMP-2 and (tissue inhibitor of metalloproteinases-2 (TIMP-2) genes variability and MS have been carried out.

The aim of this study was to investigate the possible association of MMP-2 (–168G/T, –735C/T) and TIMP-2 (+853G/A) gene polymorphisms with MS susceptibility; to find potential gender differences; and to investigate whether these polymorphisms influence disability.

Materials and methods:
A study group consisted of 240 patients fulfilling McDonald’s criteria of MS, a control group consisted of 135 healthy volunteers. Clinical status was evaluated with the Expanded Disability Status Scale (EDSS) and the disease severity was calculated using the MS Severity Score (MSSS). Polymerase chain reaction (PCR) methods and restriction analysis were used for genotyping in MMPs genes.

We demon­strated a borderline association between TIMP-2 +853G/A gene polymorphism and a risk of developing relapsing-remitting MS (Pg = 0.04), odds ratio (OR), 1.46; 95% confidence interval (CI): 0.91–2.36). Other polymorphisms were associated neither with MS susceptibility nor with the disease phenotype. No association with disability was found.

MMP-2 and TIMP-2 gene polymorphisms are not a risk factor for MS susceptibility in the Czech population.

Key words:
gene polymorphism – matrix metalloproteinases – multiple sclerosis


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