title: Tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphisms in a Caucasian population with abdominal aortic aneurysm.
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 + 16C > 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.
authors: Department of Visceral, Thoracic and Vascular Surgery, Medical School of the Technical University of Dresden, Fetscherstr, 74 D-01307 Dresden, Germany. irene.hinterseher@uniklinikum-dresden.de
authors: Irene
authors: I
authors: Hinterseher
authors: Dietmar
authors: D
authors: Krex
authors: Eberhard
authors: E
authors: Kuhlisch
authors: Karl G
authors: KG
authors: Schmidt
authors: Christian
authors: C
authors: Pilarsky
authors: Wolfgang
authors: W
authors: Schneiders
authors: Hans D
authors: HD
authors: Saeger
authors: Hendrik
authors: H
authors: Bergert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1