Polymorphism in dural arteriovenous fistula: matrix metalloproteinase-2-1306 C/T as a potential risk factor for sinus thrombosis

J Thromb Haemost. 2018 Apr;16(4):802-808. doi: 10.1111/jth.13973. Epub 2018 Mar 25.

Abstract

Essentials Sinus thrombosis may play a crucial role in development of dural arteriovenous fistula (DAVF). Little is known about the association between gene polymorphism and the development of DAVF. MMP-2-1306 C/T showed a higher prevalence rate in DAVF cases with sinus thrombosis. MMP-2-1306C/T polymorphism is likely a potential risk factor for sinus thrombosis in DAVF.

Summary: Background Dural arteriovenous fistula (DAVF) is a rare but important cerebrovascular disorder in adults. Little is known about the molecular genetic pathogenesis underlying DAVF development. Objectives To investigate the associations of gene polymorphisms and DAVF. Materials and Methods By the use of real-time PCR genotyping, seven single-nucleotide polymorphisms (SNPs) of angiogenesis-related genes were analyzed in 72 DAVF patients. Pertinent clinical and imaging data were subgrouped on the basis of location (cavernous sinus versus lateral sinus), lesions (single versus multiple), cerebral venous reflux (CVR) grading (Borden I versus Borden II/III), and sinus thrombosis (with versus without). Results We found that individuals carrying the polymorphic allele of matrix metalloproteinase (MMP)-2-1306 C/T (rs243865) had a significantly increased risk of sinus thrombosis in DAVF (odds ratio 6.2; 95% confidence interval 1.7-22.9). There was a weak difference in associations of tissue inhibitor of metalloproteinase (TIMP)-2 (rs2277698) gene polymorphism and DAVF patients subgrouped by CVR grading. Conclusions These preliminary results indicate that MMP-2-1306 C/T, but not MMP-9, TIMP-1, TIMP-2, and vascular endothelial growth factor A SNP variants, is a risk factor for the development of sinus thrombosis in DAVF patients.

Keywords: dural arteriovenous fistula; matrix metalloproteinase; single-nucleotide polymorphism; sinus thrombosis; venous hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiography, Digital Subtraction
  • Central Nervous System Vascular Malformations / diagnostic imaging
  • Central Nervous System Vascular Malformations / enzymology
  • Central Nervous System Vascular Malformations / genetics*
  • Cerebral Angiography / methods
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Magnetic Resonance Angiography
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Sinus Thrombosis, Intracranial / diagnostic imaging
  • Sinus Thrombosis, Intracranial / enzymology
  • Sinus Thrombosis, Intracranial / genetics*

Substances

  • MMP2 protein, human
  • Matrix Metalloproteinase 2