Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the risk of ischemic stroke in a Tunisian population

J Neurol Sci. 2014 Jul 15;342(1-2):107-13. doi: 10.1016/j.jns.2014.04.036. Epub 2014 May 2.

Abstract

Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, extracellular matrix remodeling, plaque rupture and myocardial infarction. MMP gene polymorphisms contribute to the risk of developing cardiovascular diseases. In this study, we investigated, for the first time, the association between MMP-1-16071G/2G, MMP-12 -82A/G and MMP-12 1082A/G genotypes and haplotypes and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). To examine whether these genetic polymorphisms are associated with susceptibility to IS, 196 patients with IS and 192 controls were examined by PCR-based RFLP. When the analyses were adjusted for multiple risk factors, no interaction between T2DM and MMP-1-1607 1G/2G polymorphism on the risk of ischemic stroke was found (p=0.074). However, MMP-12 polymorphisms genotypes were associated with the higher risk of IS in diabetic patients compared with total patients. The -82G-1082G haplotype of MMP-12 polymorphisms was associated with higher risk of ischemic stroke in diabetic patients [AOR=2.33; 95% CI (1.25-3.62), P=0.032]. These findings showed that there was an important joint effect of the MMP-12 polymorphisms and T2DM on the risk of IS and therefore it can be considered as a potential marker of cerebrovascular disorders in diabetic patients.

Keywords: Haplotype; Important joint effect; Ischemic stroke; Matrix metalloproteinases (MMPs); Polymorphism; Risk factors; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Black People / genetics*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 12 / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Stroke / complications
  • Stroke / genetics*
  • Tunisia

Substances

  • MMP12 protein, human
  • Matrix Metalloproteinase 12
  • MMP1 protein, human
  • Matrix Metalloproteinase 1