The rs9509 polymorphism of MMP-9 is associated with risk of hemorrhage in brain arteriovenous malformations

Abstract

We examined whether single nucleotide polymorphisms (SNP) of the matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 4 (TIMP-4) genes are associated with risk of intracranial hemorrhage (ICH) among patients with brain arteriovenous malformation (BAVM). For 311 Chinese patients with BAVM, we performed genotyping analysis for 11 selected SNP of MMP-9 and TIMP-4 using the MassARRAY genotyping system (Sequenom, San Diego, CA, USA). Associations between each genotype and risk of hemorrhage were evaluated using logistic regression analysis. Multivariate logistic regression analysis revealed that MMP-9_rs9509 was significantly associated with ICH among patients with BAVM with adjustments for BAVM size, venous drainage type, age and sex (adjusted odds ratio [OR]=0.19; 95% confidence interval [CI]=0.05-0.66; p=0.009 for CC compared with TT genotype). However, the association was not significant (p=0.072) after Bonferroni correction and was not significant (p=0.064) in the univariate model. The TIMP-4_rs3755724 polymorphism did not have a statistically significant effect in the multivariate model (adjusted OR=0.57; 95% CI=0.32-1.01; p=0.055 for CT compared with TT genotype). The global score test did not reveal any statistically significant differences in haplotype frequency distributions for these two genes. Our findings suggest that the MMP-9_rs9509 polymorphism may be associated with ICH in patients with BAVM.