gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

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

Meeting Abstract

  • D. Krex - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • K. Kotteck - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • I. König - Institut für Medizinische Biometrie und Statistik, Universität Lübeck
  • H. Schackert - Abteilung für Chirurgische Forschung, Universitätsklinikum Carl Gustav Carus, Technische Universität, Dresden
  • G. Schackert - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP05-03

DOI: 10.3205/09dgnc295, URN: urn:nbn:de:0183-09dgnc2958

Published: May 20, 2009

© 2009 Krex et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: There are several lines of evidence that remodeling of the extracellular matrix (ECM) is a crucial event in the pathogenesis of intracranial aneurysms (IA). Matrix-metalloproteinases (MMPs) are the most important degrading enzymes in the extracellular matrix. There are conflicting results regarding the impact of genetic variants in the pathogenesis of IA particularly in different ethnic groups. To investigate the role of genetic variants within the genes encoding MMP-2, -3, -9, and -14, we conducted a case-control study.

Methods: The entire coding regions and parts of the promoter sequences of the MMP genes were investigated using an automated laser fluorescence 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.

Results: 10, 4, 11, and 4 single nucleotide polymorphisms (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.

Conclusions: Our extensive analysis of the entire coding region of four MMPs, which are main contributors to extracellular matrix remodeling in vessel walls, 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.