gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. bis 14.05.2006, 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

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  • 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

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2006/06dgnc376.shtml

Veröffentlicht: 8. Mai 2006

© 2006 Krex et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

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.