gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

Genetic polymorphisms of homocysteine metabolism are associated with intracranial aneurysms

Assoziation zwischen genetischen Polymorphismen des Homocystein-Stoffwechsels und intrakraniellen Aneurysmata

Meeting Abstract

  • corresponding author M. Simon - Neurochirurgische Universitätsklinik, Bonn
  • A. Semmler - Neurologische Universitätsklinik, Bonn
  • D. Krex - Neurochirurgische Universitätsklinik, Dresden
  • A. Götz - Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck
  • S. Moskau - Neurologische Universitätsklinik, Bonn
  • A. Ziegler - Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck
  • M. Linnebank - Neurologische Universitätsklinik, Bonn

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocDI.02.03

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

Published: May 30, 2008

© 2008 Simon 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: Disturbances of homocysteine metabolism are associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms.

Methods: Two series of Caucasian patients harboring intracranial aneurysms (n=111 and n=144) treated at two hospitals with corresponding controls from the respective geographical areas (n=250 and n=98) were genotyped for the following genetic polymorphisms: methionine synthase (MTR) c.2756A>G, methylenetetrahydrofolate reductase (MTHFR) c.677C>T, MTHFR c.1298A>C, cystathionine beta-synthase (CBS) c.844_855ins68, CBS c.833T>C, dihydrofolate reductase (DHFR) c.594+59del19bp, glutathione S-transferase Ω-1 (GSTO1) c.428C>A, reduced folate carrier 1 (RFC1) c.80G>A, and transcobalamin 2 (Tc2) c.776C>G. Associations were investigated with stratification by center.

Results: The G-allele of Tc2 c.777C>G was found to be under-represented in aneurysma patients suggesting that this variant may protect from the formation of cerebral aneurysms (odds ratio per two risk alleles (OR) 0.48; 95% confidence interval (CI) 0.30–0.77; p=0.0024). We obtained borderline results for the G-allele of RFC1 c.80G>A (OR 1.64; 95% CI 1.01–2.65; p=0.0509) and the insertion-allele of DHFR c.594+59del19bp (OR 1.61; 95% CI 1.00-2.60; p=0.0589), which were found to be over-represented in patients.

Conclusions: Certain polymorphisms of the homocysteine metabolism are associated with the formation of intracranial aneurysms in Caucasians. These data point to a more general role for variations of homocysteine metabolism in aneurysm pathogenesis.