Genetic Factors as Promising Biomarkers of Sporadic Ascending Aortic Aneurysm

Thoracic aorta shows various changes with advancing age and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur. VR and MD are typical entities of sporadic thoracic aortic aneurysm (TAA), actually considered a common and serious health risk and a pathology by unclear mechanisms. Increased activity of the coagulation system, inflammation, activation of extracellular matrix remodeling and endothelial dysfunction pathways have been recently evidenced to have a key role in its onset. Thus, polymorphisms of the coagulation system [fibrinogen (rs1800790); Factor II ( rs1799963); Factor V (rs6025); Factor VII (rs121964926); tPA ( rs2020918); PAI-1 (rs1799768); TAFI (rs2146881)], inflammation [TLR4 (rs4986790); CCR5 (rs333)], extra-cellular matrix remodeling [MMP9 (rs3918242); MMP2 (rs243865)], endothelium dysfunction [eNOs (rs 1799983); ACE (rs1799752)] were analyzed. Methods: A total of 161 TAA individuals (127 men and 34 women; mean age: 63±10.7) and 128 controls (61 men and 67 women; mean age: 61.08±5.83 years) from Western Sicily were enrolled. Their DNA samples were genotyped for the selected polymorphisms. Results: Inconsistent associations of coagulation polymorphisms with TAA were observed while analysing preliminary data. More relevant results might be obtained when analysing their combined genotypes. Interestingly, we observed that the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA and it represents together with rs1799752 ACE, rs3918242 MMP-9 and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. Their combined risk genotype was also associated with TAA. Conclusions: Results obtained seem to suggest a new perspective for the diagnosis and prevention of sporadic TAA, utilizing genetic profiles as possible risk biomarkers.