Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis

作者：Alg Varinder S^*; Ke Xiayi; Grieve Joan; Bonner Stephen; Walsh Daniel C; Bukers Diederik; Kitchen Neil; Houlden Henry; Werring David J

来源：British Journal of Neurosurgery, 2018, 32(3): 255-259.

DOI：10.1080/02688697.2018.1427213

• Extracellular matrix
• genetics
• intracranial aneurysms
• MMP-2
• meta-analysis

Introduction: Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls.
Materials and Methods: We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C>T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP.
Results: The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33], p=.01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% 0 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p=.11).
Conclusions: Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

• 出版日期2018