GSTM1 and polycythemia: Although these variants are population-specific and rare in most patients, they underscore that heritable differences in HIF signaling can shape erythropoietic output; by analogy, carriers of HIF-pathway gain- or loss-of-function alleles could exhibit attenuated or exaggerated Hb responses (and different polycythemia risk) under pharmacologic HIF stabilization [106].