Association of Matrix Metalloproteinase-1 and Matrix Metalloproteinase-3 Gene Variants with Ischemic Stroke and Its Subtype.

BACKGROUND: Genetic variations in the genes of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of ischemic stroke (IS). Here we investigate the association between MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A genetic polymorphisms and etiological subtypes of IS in the Han Chinese population.

METHODS: A total of 640 eligible patients with IS and 637 age- and gender-matched apparently healthy volunteers were enrolled. Subtypes of IS were classified by Trial of Org 10172 in Acute Stroke Treatment criteria. MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism.

RESULTS: The frequencies of the 5A/6A + 5A/5A genotypes and 5A allele were significantly higher in patients with IS than in controls (P <.001, P <.001, respectively). No association was found between MMP-1 1G/2G polymorphism and overall IS. In subgroup analyses, MMP-1 1G/2G and 2G/2G genotypes increased the risk of small-artery occlusion (SAO) subtype (multivariate-adjusted, P <.001, P = .002, respectively), and MMP-3 5A/6A + 5A/5A genotypes were related with large-artery atherosclerosis (LAA) subtype (multivariate-adjusted, P <.001). Haplotype analyses indicated that 2G-6A and 1G-5A increased the risk of SAO (multivariate-adjusted, P = .029) and LAA (multivariate-adjusted, P <.001), respectively.

CONCLUSIONS: MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms may contribute to different subtypes of IS susceptibility.