The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms.
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.
Pannu
Hariyadarshi
H
Department of Internal Medicine and Neurosurgery, The University of Texas Medical School at Houston, USA.
Kim
Dong H
DH
Guo
Dongchuan
D
King
Terri M
TM
Van Ginhoven
Grace
G
Chin
Toinette
T
Chang
Katherine
K
Qi
Yuhua
Y
Shete
Sanjay
S
Milewicz
Dianna M
DM
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
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9