A further example of a pathogenic RiboSNitch and its potential use in personalized medicine is represented by the SNP rs12455792, localized in the 5′UTR of the SMAD4, a gene involved in blood vessel remodeling and matrix maintenance. Wang et al. demonstrated that the CT or TT genotypes were associated with reduced transcriptional activity, altered RNA folding structure, and decreased SMAD4 expression, as well as significantly elevated risk of thoracic aortic aneurysm and dissection (TAAD). Moreover, using computational analysis and other approaches, they showed that the lower SMAD4 expression might be due to a reduced function of a RNA hairpin structure. Additionally, SMAD4 mRNA abundance, assessed in freshly frozen aorta tissues from TAAD patients, was significantly higher in CC genotype than in CT or TT genotypes, suggesting rs12455792 as a predictor of TAAD progression.90
