gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Single Nucleotide Polymorphism in A20 gene regulates TNFalpha expression in atherosclerotic plaque

Meeting Abstract

  • Gabor Gäbel - Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden
  • Lesca M. Holdt - Universitätsklinikum Leipzig, Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Leipzig
  • Irene Hinterseher - Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden
  • Daniel Teupser - Universitätsklinikum Leipzig, Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Leipzig
  • Hendrik Bergert - Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch574

DOI: 10.3205/11dgch574, URN: urn:nbn:de:0183-11dgch5746

Veröffentlicht: 20. Mai 2011

© 2011 Gäbel 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 vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Up-regulation of inflammatory responses is considered a driving force of atherosclerotic lesion development. Nuclear factor (NF)-kB plays a major role in regulating these inflammatory processes. Multiple mechanisms normally ensure proper termination of NF-kB activation. In this context, the intracellular ubiquitin-editing protein A20 is a key player in the negative feedback regulation of NF-kB signalling in response to multiple stimuli. The possibility that A20 and reduction in NF-kB activity might modulate risk of atherosclerosis was suggested by findings of linkage between the A20 gene region and atherosclerosis in an intercross between atherosclerosis-susceptible and –resistant mice.

The aim of our study was to determine whether genetic variability at the A20 locus modulates TNFa expression in the atherosclerotic plaque.

Materials and methods: Atherosclerotic lesions from 172 patients have been collected intraoperativly (71 patients with severe stenosis of the internal carotid artery; 63 patients with peripheral artery disease; 38 patients with aortic aneurysm). DNA and RNA were isolated from the plaque. TNFa mRNA-expression was determined by quantitative RT-PCR. Genotyping of known single nucleotide polymorphisms (SNPs) in the A20 gene was performed.

Results: A non-coding SNP (rs610604) in the A20 gene had significant influence on TNFa expression. Wildtype patients (230.9 ± 28.2; p<.05) showed significant lower TNFa expression in the atherosclerotic plaque than heterozygotes (296.1 ± 43.8) and minor allele homozygotes (658.4 ± 224.2).

Conclusion: We identified a non-coding SNP (rs610604) in the exon of the A20 gene that causes increased TNFa expression. We suppose this is mediated by allelic differences in A20 expression. If A20 polymorphisms influence the atherosclerosis risk in the general population needs to be determined by future studies.