title: The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine and Neurosurgery, The University of Texas Medical School at Houston, USA.
authors.forename: Hariyadarshi
authors.initials: H
authors.lastname: Pannu
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kim
authors.forename: Dongchuan
authors.initials: D
authors.lastname: Guo
authors.forename: Terri M
authors.initials: TM
authors.lastname: King
authors.forename: Grace
authors.initials: G
authors.lastname: Van Ginhoven
authors.forename: Toinette
authors.initials: T
authors.lastname: Chin
authors.forename: Katherine
authors.initials: K
authors.lastname: Chang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Qi
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
mesh_terms: D005260:Female; D006239:Haplotypes; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013345:Subarachnoid Hemorrhage / Q000235:genetics
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9