Genotyping strategy of SMAD-3 rs3825977 gene variant for a differential management of ascending aorta aneurysm in women people: Gender oriented diagnostic tools

Background and objectives: The research of opportune strategies for facilitating the management of complex pathologies, such as ascending aorta aneurysm (AAA), currently represents the principal object of clinicians, clinical pathologists included. Herein, we propose genotyping of gene variants related to TGF-β pathway as useful strategy to improve the complex AAA management, exclusively based on imaging evaluations. Precisely, we investigated four functional SNPs in SMAD and VEGF genes, encoding molecules able to modulate functions and cross-talks of TGF-β pathway. Populations and methods: Our study included 92 individuals (70 men (76%) and 22 (24%) women; mean age: 71.4 ± 2.6 years) affected by sporadic AAA, and two age/gender matched control groups. Kaspar PCR genotyping and opportune histopathological/immune-histochemical techniques were used. Results: Interestingly, we evidenced a significant association of CT + TT genotypes of SMAD3 rs3825977 gene variant with a higher AAA risk in women patients. CT + TT genotypes of SMAD3 rs3825977 gene variant positively correlated with the major conventional risk factors of AAA, a higher tissue aorta levels of metalloproteinase (MMP)-9 and a higher significant medial degeneration characterized by a higher grade of severity in elastic fragmentation. To the best of our knowledge, this is the first study on the association and relationship between SMAD3 rs3825977 gene variant and AAA. Several crucial aspects remain, however, to clear. Conclusions: We believe that further investigations, such as the analysis of SMAD3 gene transcripts and tissue proteins are imperative.