Given the distinctive patterns of three key biomarkers of PAH in our study, we speculate that in the early phase of PAH (mild-to-moderate PAH), the physiologic response of endothelin-1 still exists, such that the therapy with endothelin-1 receptor antagonists is important to reduce pulmonary artery pressure in early PAH. The gene discussed is EDNRA; the disease is pulmonary arterial hypertension.