Gender-specific effects of MMP-2 and MMP-9 gene variants and the risk of aneurysmal subarachnoid haemorrhage

Matrix metalloproteinases (MMPs), a family of zinc-dependent proteases, have been linked with the pathogenesis of intracranial aneurysm (IA) formation and rupture. Patients with IA have elevated serum levels of MMP-2 and MMP-9 gene expression has been shown to be increased in aneurysm tissue. In this study, we have evaluated the association between MMP gene variants and aneurysmal subarachnoid hemorrhage (aSAH). The rs243865 in MMP-2 and rs17576 in MMP-9 genes were genotyped using Taqman allelic discrimination assay. Upon gender stratification, the presence of G allele of MMP-9 gene exon variant was found to increase the risk of aSAH by 1.4 fold (p = 0.032), in men. The GG genotype also showed a trend towards association with the risk of aSAH (OR: 1.785, CI: 0.971-3.283, p = 0.062) in men, after adjusting for the vascular risk factors. In women, no association was observed. The MMP-2 gene variants were not associated with aSAH in both genders. Further functional studies are required to describe the exact basis of the association between MMP-9 polymorphism and intracranial aneurysm in men.