• Hariyadarshi Pannu, Dong H Kim, Dongchuan Guo, Terri M King, Grace Van Ginhoven, Toinette Chin, Katherine Chang, Yuhua Qi, Sanjay Shete, and Dianna M Milewicz.
• Department of Internal Medicine and Neurosurgery, The University of Texas Medical School at Houston, USA.
• J. Neurosurg. 2006 Sep 1; 105 (3): 418-23.

ObjectMatrix 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.MethodsEight 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.ConclusionsThe study findings support a role for MMP-9, but not MMP-2, in the pathogenesis of intracranial aneurysms.

18 keywords...

hide…