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

Br J Neurosurg. 2018 Jun;32(3):255-259. doi: 10.1080/02688697.2018.1427213. Epub 2018 Jan 15.

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.

Keywords: Extracellular matrix; MMP-2; genetics; intracranial aneurysms; meta-analysis.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aneurysm, Ruptured / genetics*
  • Case-Control Studies
  • Extracellular Matrix / metabolism
  • Female
  • Genetic Association Studies
  • Genetic Variation / genetics*
  • Humans
  • Hypertension / complications
  • Intracranial Aneurysm / genetics*
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Reference Values
  • Risk Factors
  • Smoking / adverse effects
  • Transcription, Genetic / genetics

Substances

  • Matrix Metalloproteinase 2