Further investigations are needed, but our findings may reflect the complicated balance of BMPR2, the TGFβ pathway and associated events that result in PAH among susceptible subjects (such as those with low BMPR2 at baseline), or the possibility that Smad-independent effects mediate downstream ramifications of BMPR2 gene expression changes. The gene discussed is TGFB1; the disease is pulmonary arterial hypertension.