Although the etiology of aortic aneurysm is assumed to be multifactorial, genetic influences appear to be independently associated with both disease states. A genetic predisposition to abdominal aortic aneurysm development is demonstrated by clustering of aneurysms in families and has been documented by both familial and segregation observational studies [31–33]. Baird et al. found an aneurysm prevalence of 19 % in siblings of patients with abdominal aortic aneurysm as compared to 8 % in controls using ultrasound examination, and the risk of aneurysm was demonstrated to begin earlier and increase more rapidly for siblings of affected individuals compared with controls [32]. Several investigators have also followed a candidate gene approach to further characterize the genetic component in aneurysm pathogenesis. Thompson et al. have undertaken a meta-analysis of all aneurysm candidate gene analysis studies and identified three polymorphisms associated with a significant risk of aneurysm [ACE RR 1.33 (95 % CI 1.20–1.48), MTHFR RR 1.14 (1.08–1.21), and MMP-9 RR 1.09 (1.01–1.18)] [34]. Genes encoding the components of the extracellular matrix as well as those involved in mechanisms of connective tissue metabolism and inflammatory response have been extensively investigated. In particular, polymorphic sites and gene mutations of proteins of the structural components of the connective tissue (elastin, collagen), extracellular matrix-degrading enzymes and their inhibitors (MMPs, TIMPs), and inflammation promotion agents (interleukins, platelet-activating factor, nitric oxide synthase, inflammatory receptors) have been investigated separately in gene association observational studies. Nevertheless, no single gene has yet been isolated as the key factor interpreting the genetic basis of aortic aneurysm. A small number of families have a genetically determined type III collagen defect (COL3A1), in which cases the abdominal aortic aneurysm is considered to be a manifestation of Ehlers-Danlos syndrome [35]. Furthermore, mutations in the fibrilin-1 gene (15q21.1), resulting in abnormal fibrilin-1 synthesis, secretion, or use, are responsible for Marfan syndrome, which is a hereditary connective tissue disorder associated with thoraco-­abdominal aortic aneurysms and dissections [36].

Pharmacotherapeutic approaches to prevent or slow down the development and progression of the disease constitute a virgin field in medical research. Targeted approaches with the design of specific inhibitors of key players in the connective tissue degeneration process might provide novel pharmacological methods to decelerate aneurysm progression. Further knowledge about mechanisms of regulation of MMP gene expression may direct therapeutic strategies toward tissue-targeted gene therapies with agents that selectively inhibit specific MMPs.