The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms

J Neurosurg. 2006 Sep;105(3):418-23. doi: 10.3171/jns.2006.105.3.418.


Object: Matrix metalloproteinases (MMPs) are a family of endopeptidases that mediate vascular remodeling by degrading extracellular matrix components, such as collagen and elastin. On the basis of accumulating evidence that implicates increased MMP-2 (gelatinase A) and MMP-9 (gelatinase B) amounts and activity in the pathogenesis of aneurysms, the authors investigated the genetic association between polymorphisms in MMP-2 and MMP-9 and sporadic intracranial aneurysms.

Methods: Eight polymorphisms located in MMP-2 and MMP-9 were genotyped, and the association of these variations with disease was assessed in a Caucasian population consisting of 125 patients with intracranial aneurysms and 234 ethnically matched healthy volunteers. Polymorphisms in the MMP-2 gene and the haplotypes generated from these polymorphisms were not associated with the occurrence of intracranial aneurysms. However, a polymorphism located in the 3' untranslated region of MMP-9 showed a significant association with disease in the study population, with individuals carrying the TT genotype at increased risk for developing intracranial aneurysms (odds ratio 1.91, p = 0.005). Haplotypes containing the T allele of this polymorphism also showed a comparable association with disease. Similar results were obtained in an analysis of these polymorphisms in a subgroup of patients who presented with ruptured aneurysms.

Conclusions: The study findings support a role for MMP-9, but not MMP-2, in the pathogenesis of intracranial aneurysms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Female
  • Haplotypes
  • Humans
  • Intracranial Aneurysm / genetics*
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Microsatellite Repeats
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Subarachnoid Hemorrhage / genetics


  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9