Analyse von genvarianten des gewebeinhibitors der metalloproteinase-2 (TIMP-2) bei patienten mit abdominalem aortenaneurysma
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Contributors
Abstract
Background: The formation of sporadic abdominal aortic aneurysm (AAA) is explained by a remodelling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinases are the principle matrix-degrading proteases and are known to play a major role in the remodelling of the extracellular matrix in arterial vessels. Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). Decreased TIMP-1 and TIMP-2 expression in the extracellular matrix of the walls of AAAs has been demonstrated in several studies. This case-control study was designed to investigate the possible impact of genetic variants of the TIMP-2 gene in the aetiology of AAA and to reproduce a recently described significant difference in allele frequency of the SNP 303Gcombining low line>A in a German population. Methods: TIMP-2 single nucleotide polymorphisms (SNPs) were analysed in a study sample of 50 patients with AM and 41 controls. Differences in genotype and allele frequencies of the identified polymorphisms were determined after sequencing the entire coding region and selected parts of the promoter using the automated laser fluorescence technique. Results: Six polymorphisms were identified, one of which is described for the first time, located in the intron, (231 + 23Ccombining low line > T). An association of the SNP 303Gcombining low line > A with the phenotype was not confirmed in our study (p = 0.648). However, the CT genotype of the SNP -479Ccombining low line > T was more frequent in patients with AAA than in the control group (p = 0.054). Conclusions: In our analysis of the TIMP-2 gene, we identified one new SNP. A previously published association of the SNP 303Gcombining low line > A with the phenotype could not be validated in our population. However, we detected an association for the CT genotype of one polymorphism in the promoter region (g-479Ccombining low line > T) and AAA. This result has to be proved in a second study sample.
Translated title of the contribution | Analysis of tissue inhibitor of metalloproteinase-2 gene polymorphisms in a caucasian population with abdominal aortic aneurysms |
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Details
Original language | German |
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Pages (from-to) | 332-337 |
Number of pages | 6 |
Journal | Zentralblatt fur Chirurgie - Zeitschrift fur Allgemeine, Viszeral- und Gefasschirurgie |
Volume | 133 |
Issue number | 4 |
Publication status | Published - Aug 2008 |
Peer-reviewed | Yes |
External IDs
PubMed | 18702016 |
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Keywords
ASJC Scopus subject areas
Keywords
- Abdominal aortic aneurysm, Genetics, Polymorphism, TIMP-2