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Background  Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis and neurovascular remodelling during the delayed neuroinflammatory response phase, thus possibly contributing to stroke functional recovery.    Methods  In the present study, the role of  MMP-2  and  MMP-9  genetic variants in stroke recovery was investigated in 546 stroke patients. Functional outcome was assessed three months after a stroke episode using the modified Rankin Scale (mRS), and patients were classified in two groups: good recovery (mRS ≤ 1) or poor recovery (mRS>1). Haplotype tagging single nucleotide polymorphisms (SNPs) in the  MMP-2  (N = 21) and  MMP-9  (N = 4) genes were genotyped and tested for association with stroke outcome, adjusting for significant non-genetic clinical variables.    Results  Six SNPs in the  MMP-2  gene were significantly associated with stroke outcome (0.0018< P  < 0.0415), two of which survived the Bonferroni correction for multiple testing. In the subset of ischemic stroke patients, association of five of these SNPs remained positive (0.0042< P  < 0.0306). No significant associations were found for the  MMP-9  gene.    Conclusions  The results presented strongly indicate that  MMP-2  genetic variants are an important mediator of functional outcome after stroke.

Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase-9 genes significantly influence functional outcome after stroke