gms | German Medical Science

66th Annual Meeting of the German Society of Neurosurgery (DGNC)
Friendship Meeting with the Italian Society of Neurosurgery (SINch)

German Society of Neurosurgery (DGNC)

7 - 10 June 2015, Karlsruhe

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ADAMTS-genes and risk of cerebral aneurysm

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  • Astrid Arning - Institut für Humangenetik, Genetische Epidemiologie, Universität Münster
  • Astrid Jeibmann - Institut für Neuropathologie, Universitätsklinikum Münster
  • Stephan Köhnemann - Institut für Rechtsmedizin, Universitätsklinikum Münster
  • Benjamin Brokinkel - Klinik für Neurochirurgie, Universitätsklinikum Münster
  • Christian Ewelt - Klinik für Neurochirurgie, Universitätsklinikum Münster
  • Klaus Berger - Institut für Epidemiologie und Sozialmedizin, Universität Münster
  • Jürgen Wellmann - Institut für Epidemiologie und Sozialmedizin, Universität Münster
  • Rita Hagel - Institut für Humangenetik, Genetische Epidemiologie, Universität Münster
  • Ulrike Nowak-Göttl - Institut für Klinische Chemie, Gerinnungszentrum Kiel, Universitätsklinikum Kiel
  • Walter Stummer - Klinik für Neurochirurgie, Universitätsklinikum Münster
  • Monika Stoll - Institut für Humangenetik, Genetische Epidemiologie, Universität Münster
  • Markus Holling - Klinik für Neurochirurgie, Universitätsklinikum Münster

Deutsche Gesellschaft für Neurochirurgie. 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Karlsruhe, 07.-10.06.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocP 141

doi: 10.3205/15dgnc539, urn:nbn:de:0183-15dgnc5399

Published: June 2, 2015

© 2015 Arning et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Cerebral aneurysms (IAs) affect 2-5% of the population and familial predisposition plays a significant role in IA pathogenesis. Several lines of evidence suggesting that genetic variations in different genes of matrix metalloproteinases (MMPs) are involved in the etiopathology of IAs. Here, we performed a case-control study to investigate the effect of certain candidate variants in four MMP-genes of the ADAMTS gene family of IAs pathogenesis.

Method: To identify susceptible genetic variants, 8 single nucleotide polymorphisms (SNPs) in four different genes from the ADAMTS gene family (ADAMTS-2, -7, -12 & -13) known to be associated with vascular diseases were investigated in our study population of 353 patients and 1055 controls.

Results: Significant associations between variants in three members of the ADAMTS metalloproteinases family and IA susceptibility were found. The largest risk of a single variant (1.31; p=0.006) was observed for carriers of variant rs11750568 in ADAMTS2, associated with pediatric stroke. Three SNPs under study suggesting a protective effect in IA pathogenesis (rs1364044 (ADAMTS12) OR: 0.65, p=0.0001; rs739469 and rs4962153 (ADAMTS13) OR:0.76 and 0.63, p=0.02 and p=0.0006 ) whereas the two other susceptibility variants in ADAMTS13 may confer a significant risk (rs2301612; OR:1.25; p=0.011; rs2285489; OR:1.24;p=0.02).

Conclusions: Although mechanisms of action remain unknown, results give rise to the hypothesis that a disposition towards a reduced integrity of the endothelial wall conferred by ADAMTS variations together with inflammatory processes and defective vascular remodeling play an important role in IA pathogenesis. Our findings may lead to specific screening of risk populations in the future.