Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase-9 genes significantly influence functional outcome after stroke.
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.
Manso
Helena
H
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Krug
Tiago
T
Sobral
João
J
Albergaria
Isabel
I
Gaspar
Gisela
G
Ferro
José M
JM
Oliveira
Sofia A
SA
Vicente
Astrid M
AM
D000328:Adult; D001921:Brain / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9