| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>In the present study, the role of <it>MMP-2 </it>and <it>MMP-9 </it>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 <it>MMP-2 </it>(N = 21) and <it>MMP-9 </it>(N = 4) genes were genotyped and tested for association with stroke outcome, adjusting for significant non-genetic clinical variables.</p> <p>Results</p> <p>Six SNPs in the <it>MMP-2 </it>gene were significantly associated with stroke outcome (0.0018<<it>P </it>< 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<<it>P </it>< 0.0306). No significant associations were found for the <it>MMP-9 </it>gene.</p> <p>Conclusions</p> <p>The results presented strongly indicate that <it>MMP-2 </it>genetic variants are an important mediator of functional outcome after stroke.</p>
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