Hinterseher I, Krex D, Kuhlisch E, Pilarsky C, Schneiders W, Saeger H D, Bergert H
Klinik und Poliklinik für Viszeral-, Thorax und Gefässchirurgie, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Germany.
Zentralbl Chir. 2008 Aug;133(4):332-7. doi: 10.1055/s-2008-1076862.
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 303G>A in a German population.
TIMP-2 single nucleotide polymorphisms (SNPs) were analysed in a study sample of 50 patients with AAA 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.
Six polymorphisms were identified, one of which is described for the first time, located in the intron, (231+23C>T). An association of the SNP 303G>A with the phenotype was not confirmed in our study (p=0.648). However, the CT genotype of the SNP -479C>T was more frequent in patients with AAA than in the control group (p=0.054).
In our analysis of the TIMP-2 gene, we identified one new SNP. A previously published association of the SNP 303G>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-479C>T) and AAA. This result has to be proved in a second study sample.
散发性腹主动脉瘤（AAA）的形成可通过细胞外基质（ECM）重塑和血管壁结构成分破坏来解释。基质金属蛋白酶是主要的基质降解蛋白酶，已知在动脉血管细胞外基质重塑中起主要作用。其活性受金属蛋白酶组织抑制剂（TIMPs）控制。多项研究已证实AAA壁细胞外基质中TIMP-1和TIMP-2表达降低。本病例对照研究旨在调查TIMP-2基因遗传变异在AAA病因学中的可能影响，并在德国人群中重现最近描述的单核苷酸多态性（SNP）303G>A等位基因频率的显著差异。
在50例AAA患者和41例对照的研究样本中分析TIMP-2单核苷酸多态性（SNP）。使用自动激光荧光技术对整个编码区和启动子的选定部分进行测序后，确定已鉴定多态性的基因型和等位基因频率差异。
鉴定出6种多态性，其中一种首次描述，位于内含子中（231+23C>T）。我们的研究未证实SNP 303G>A与表型的关联（p=0.648）。然而，SNP -479C>T的CT基因型在AAA患者中比对照组更常见（p=0.054）。
在我们对TIMP-2基因的分析中，我们鉴定出一种新的SNP。先前发表的SNP 303G>A与表型的关联在我们的人群中无法得到验证。然而，我们检测到启动子区域一种多态性（g-479C>T）的CT基因型与AAA有关联。这一结果必须在第二个研究样本中得到证实。
