Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

P H C Kremer, B P C Koeleman, G Je Rinkel, F P Diekstra, L H van den Berg, J H Veldink, C J M Klijn

Research output: Contribution to journalArticleAcademicpeer-review


Background Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. Methods We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by Χ<sup>2</sup> testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3. Results In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1β, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). Conclusions The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1β, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis.

Original languageEnglish
Pages (from-to)693-6
Number of pages4
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number7
Publication statusPublished - Jul 2016


  • Adult
  • Angiopoietin-Like Protein 4
  • Angiopoietins/genetics
  • Case-Control Studies
  • Female
  • Gene Frequency/genetics
  • Genetic Loci/genetics
  • Genetic Predisposition to Disease/genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Interleukin-1beta/genetics
  • Intracranial Arteriovenous Malformations/genetics
  • Male
  • Matrix Metalloproteinase 3/genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide/genetics
  • Receptors, G-Protein-Coupled/genetics
  • Reproducibility of Results
  • Vascular Endothelial Growth Factor A/genetics


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