gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Genetic variants of genes encoding for extracellular matrix enzymes in the pathogenesis of intracranial aneurysms

Genetische Varianten in Genen, die für Enzyme der extrazellulären Matrix kodieren, in der Pathogenese von intrakraniellen Aneurysmen

Meeting Abstract

  • corresponding author D. Krex - Klinik für Neurochirurgie, Universitätsklinikum Dresden
  • S. Fortun - Klinik für Neurochirurgie, Universitätsklinikum Dresden
  • I. R. König - Chirurgische Forschung, Universitätsklinikum Dresden
  • A. Ziegler - Chirurgische Forschung, Universitätsklinikum Dresden
  • H. K. Schackert - Chirurgische Forschung, Universitätsklinikum Dresden
  • G. Schackert - Chirurgische Forschung, Universitätsklinikum Dresden

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP071

The electronic version of this article is the complete one and can be found online at:

Published: May 4, 2005

© 2005 Krex et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.




There are several lines of evidence that remodelling of the extracellular matrix (ECM) is a crucial event in the pathogenesis of cerebral aneurysms. Matrix-metalloproteinases (MMPs) are the most important degrading enzymes in the extracellular matrix. In addition, NO, synthesized by the endothelial isoform of nitric oxide synthase (eNOS) plays an essential role in the ECM. To investigate the possible impact of genetic variants within the genes encoding MMP-2, -3, -9, and -14, and eNOS, respectively, we conducted a case-control study.


The entire coding regions and parts of the promoter sequences of the MMP genes were investigated using the automated laser fluorescence (A.L.F.) technique. Genotypes and allele frequencies were determined in a primary study sample comprising 44 well defined aneurysm patients and 40 controls. Those being in Hardy-Weinberg disequilibrium were analyzed in another sample of 40 cases and 40 controls, respectively. Odds ratios (ORs) and exact 95% confidence intervals (CIs) were calculated to compare allele frequencies and genotype frequencies using the Cochrane-Armitage trend test. For the analysis of the eNOS gene, 3 genomic regions comprising 4 genetic variants were directly sequenced in 142 cases and 190 controls.


10, 4, 11, and 4 single nucleotide polymorphism (SNPs) were identified in MMP-2, -3, -9, and -14 genes, respectively. Deviations from Hardy-Weinberg equilibrium were particularly found for MMP-2 and MMP-9 SNPs, however, there were no significant differences in genotype and allele frequencies in those or between any of the other groups. Likewise, there was no significant difference in allele frequencies between cases and controls in any of the four eNOS genetic variants.


Our analysis of the entire coding region of four MMPs, which are main contributors to extracellular matrix remodelling in vessel walls, and genetic variants of the eNOS gene known to be associated with other vascular diseases, failed to show an association of genetic polymorphisms with an intracranial aneurysm. However, deviations from Hardy Weinberg equilibrium found for MMP-2, and MMP-9, but also for MMP-3, suggest that there might be additional more distantly located genetic variants of functional impact, which are the subject of ongoing studies.