Low iron treatment significantly increases EPO expression and exacerbates the polycythemia of Irp1-/- mice, which could be attributed to the stabilization of HIF2α by iron deficiency; in contrast, the iron-deficient diet did not exacerbate the pulmonary hypertension of Irp1-/- mice, and the endothelin-1 levels were not altered either, suggesting that there are mechanistic differences in the pathophysiology of polycythemia and pulmonary hypertension. The gene discussed is EPAS1; the disease is nutritional disorder.