gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

The impact of epigenetic inactivation of extracellular matrix components in the pathogenesis of intracranial aneurysms

Die Bedeutung der epigenetischen Inaktivierung von Komponenten der extrazellulären Matrix in der Pathogenese intrakranieller Aneurysmen

Meeting Abstract

  • corresponding author D. Krex - Klinik für Neurochirurgie, Universitätsklinik Carl Gustav Carus, Technische Universität Dresden
  • R. Küster - Klinik für Neurochirurgie, Universitätsklinik Carl Gustav Carus, Technische Universität Dresden
  • L. Hesson - Section of Medical and Molecular Genetics, University of Birmingham, UK
  • G. Schackert - Klinik für Neurochirurgie, Universitätsklinik Carl Gustav Carus, Technische Universität Dresden

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 10.159

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

Published: May 8, 2006

© 2006 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.



Objective: The wall of intracranial aneurysms (IA) is characterized by numerous structural variations. Particularly components of the extracellular matrix are insufficiently or defectively produced, and there is an increased activity of degrading enzymes leading to a less resistant and less elastic vessel wall. These altered enzyme activities are based on an altered gene product, which commonly might be due to genetic variants or epigenetic inactivation. The latter might occur not only in the germ-line, but also in situ. In the present study we investigated, whether genes, encoding for structural proteins or metabolizing enzymes within the extracellular matrix in intracranial aneurysms are inactivated by promoter hypermethylation.

Methods: FBN1, FBN2, PKD1, PKD2, MMP2, TIMP3 have been selected for analysis. There are numerous CpG island within the potential promoter region of the encoding genes susceptible for hypermethylation. Genomic DNA was isolated from aneurysm tissue from 28 IA patients (12 male, 16 female; median age 50 and 59 years, respectively), and from 9 arteria cerebri media samples, post-mortem taken from patients without IA. DNA was bisulphit treated and a total of ten genomic regions were amplified by methylation specific primers. Methylation status was determined by direct sequencing of the PCR product using the ALF® sequence analyzer equipment.

Results: All analyzed genes were not methylated in normal arterial tissue. About 15% of all analyzed CpG islands of the promoter region of FBN2 were found to be methylated in all IA samples. There was no difference between IA and normal tissue in the promoter methylation pattern for the FBN1, PKD1, PKD2, MMP2, TIMP3 genes.

Conclusions: In situ epigenetic inactivation by promoter hypermethylation is not a common tool for the impairment of genes encoding for structural proteins end important enzymes of the extracellular matrix of IA.