Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis. (4th May 2018)

• Record Type: Journal Article
• Authors: Alg, Varinder S.; Ke, Xiayi; Grieve, Joan; Bonner, Stephen; Walsh, Daniel C.; Bulters, Diederik; Kitchen, Neil; Houlden, Henry; Werring, David J.
• Is Part Of: British journal of neurosurgery. Volume 32:Number 3(2018)
• Page Start: 255
• Page End: 259
• Publication Date: 2018-05-04
• Subjects: Extracellular matrix -- genetics -- intracranial aneurysms -- MMP-2 -- meta-analysis; Nervous system -- Surgery -- Periodicals; 617.48
• DOI: 10.1080/02688697.2018.1427213
• Languages: English
• ISSNs: 0268-8697

Abstract

Abstract: 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% CI 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.