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Open Access 01-12-2010 | Research article

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

Authors: Helena Manso, Tiago Krug, João Sobral, Isabel Albergaria, Gisela Gaspar, José M Ferro, Sofia A Oliveira, Astrid M Vicente

Published in: BMC Medical Genetics | Issue 1/2010

Abstract

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/11/40/prepub

Title: Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase-9 genes significantly influence functional outcome after stroke
Authors: Helena Manso
Tiago Krug
João Sobral
Isabel Albergaria
Gisela Gaspar
José M Ferro
Sofia A Oliveira
Astrid M Vicente
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2010
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-11-40

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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