A possible hypothesis would be that in younger patients, where the role of aging and classic atherosclerosis risk factors are weaker, PNPLA3 can fully exert its atherogenic role; in older patients, as effect of PNPLA3-induced liver disease progression, the reduction of LDL levels (115.1±38.6 mg/dl in F3–F4 vs. 128.9±38.2 mg/dl in F0–F2 Sicilian cohort) [29] and arterial pressure values associated with advanced liver disease might counterbalance the potential atherogenic role of the PNPLA3 genotype, vanishing the differences in IMT of the different polymorphisms. The gene discussed is PNPLA3; the disease is atherosclerosis.