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World Journal of Surgery

, Volume 31, Issue 11, pp 2248–2254 | Cite as

Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Polymorphisms in a Caucasian Population with Abdominal Aortic Aneurysm

  • Irene Hinterseher
  • Dietmar Krex
  • Eberhard Kuhlisch
  • Karl G. Schmidt
  • Christian Pilarsky
  • Wolfgang Schneiders
  • Hans D. Saeger
  • Hendrik Bergert
Article

Abstract

Background

The formation of a sporadic abdominal aortic aneurysm (AAA) is explained by the remodeling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinases are the principal matrix-degrading proteases and are known to play a major role in the remodeling 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 shown in several studies. This case control study was designed to investigate the possible impact of genetic variants of the TIMP-1 gene in the etiology of AAA.

Methods

TIMP-1 single nucleotide polymorphisms (SNPs) were analyzed in a primary study sample of 50 patients with AAA and 44 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined after sequencing the entire coding region and selected parts of the promoter using the automated laser fluorescence technique. A second sample (96 patients vs. 89 controls) was investigated by single-base sequencing to confirm significant results.

Results

Three polymorphisms were identified, one of which, described for the first time in this article, is located in intron 4 (TIMP-1: 328 + 16> T). A statistically significant difference in allele frequencies for SNP TIMP-1 372T>C was detected in the primary study group. The C allele was more frequent in male patients with AAA than in the control group [23 vs. 4, p = 0.029, OR (95% CI) 4.38 (1.13-20.47)]. However, this result could not be confirmed in a second sample of males [52 vs. 45, p = 0.624, OR (95% CI) 1.16 (0.65-2.06)]. There were no statistically significant differences in genotype or allele frequencies of the other detected SNPs between the two groups.

Conclusions

Our analysis of the entire coding region and selected parts of the promoter of the TIMP-1 gene failed to show an association between genetic polymorphisms and AAA, suggesting that variations in the TIMP-1 gene do not contribute to the development of AAA.

Keywords

Abdominal Aortic Aneurysm Abdominal Aortic Aneurysm Marfan Syndrome Entire Code Region Infrarenal Abdominal Aortic Aneurysm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Société Internationale de Chirurgie 2007

Authors and Affiliations

  • Irene Hinterseher
    • 1
  • Dietmar Krex
    • 2
  • Eberhard Kuhlisch
    • 3
  • Karl G. Schmidt
    • 4
  • Christian Pilarsky
    • 1
  • Wolfgang Schneiders
    • 1
  • Hans D. Saeger
    • 1
  • Hendrik Bergert
    • 1
  1. 1.Department of Visceral, Thoracic and Vascular SurgeryMedical School of the Technical University of DresdenFetscherstrGermany
  2. 2.Department of NeurosurgeryTechnical University of DresdenDresdenGermany
  3. 3.Department of Medical Statistics and BiometryTechnical University of DresdenDresdenGermany
  4. 4.Department of OphthalmologyTechnical University of DresdenDresdenGermany

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