SMAD4 and obstructive sleep apnea syndrome: In conclusion, our study shows that patients with severe OSA present an overexpression of SMAD4, induced both by intermittent hypoxaemia and circadian rhythm deregulation secondary to sleep fragmentation, reflecting greater activity of the TGFβ/SMAD pathway, and this being a risk factor for the presence of some comorbidities that involve TGFβ in their pathogenesis (Figure 7).