Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

Abstract

Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.

Matrix Metalloproteinase 2 Polymorphisms in a Caucasian Population with Abdominal Aortic Aneurysm

“…Therefore, MMP2 polymorphisms do not contribute to the onset of sporadic AAA in our Caucasian population. These results are corroborated by that of a recent study by Ogata et al [27]. Despite the striking evidence that ECM remodeling enzymes might contribute to AAA development, the present study and results by others [27][28][29][30][31] failed to support the hypothesis that matched controls with similar risk factors (smoking, hypertension), but without AAA.…”

“…Various candidate genes (IL-6, TIMP-1, TIMP-2, MMP3, MMP9, PAI-1) have been investigated in different ethnic groups to identify an association between a genetic variant and the sporadic AAA phenotype [27][28][29][30][31]. These investigations have been based upon the observation that there is extensive destruction of the ECM in the wall of the aneurysm.…”

“…There are several lines of evidence suggesting that an altered balance in the activity of proteases and protease inhibitors is a main cause of the observed ECM degradation [13,14,16,17,24,29,32,33]. Most recently, Ogata et al have shown the importance of the role of the TIMP1 gene in the development of AAA [27].…”

Angiotensin-Converting Enzyme (ACE, I/D) Gene Polymorphism and Susceptibility to Abdominal Aortic Aneurysm or Aortoiliac Occlusive Disease

“…Abdominal aortic aneurysm (AAA) is a life threatening chronic condition affecting approximately 1% to 6% of the population in developed countries [1][2][3]. Pathogenesis of AAA is considered to be a multifactorial process with both genetic and environmental risk factors [4,5].…”

“…Pathogenesis of AAA is considered to be a multifactorial process with both genetic and environmental risk factors [4,5]. Abdominal aortic aneurysms are characterized by histological signs of chronic inflammation, destruction of elastin and collagen in the media and adventitia, smooth muscle cell depletion with thinning of the medial wall, and neovascularization [1][2][3]6].…”