Hemoglobinopathies

Information about the genetics underlying heritable hemoglobinopathy subphenotypes could inform prognosis and the use of personalized therapies. Therefore, investigators from the ICMR-National Institute of Immunohaematology, Mumbai, India, evaluated genetic modifiers leading to higher fetal hemoglobin (HbF) production in β-thalassemia and sickle cell disease, along with their impact on disease severity. The study included 100 patients with β-thalassemia (homozygotes) and 100 with sickle cell anemia (confirmed by molecular analysis), plus 50 healthy controls. The researchers screened for coexisting α-thalassemia and the polymorphisms located in 3 genetic loci linked to HbF regulation. "The most remarkable result," they wrote, "was the association of SNPs with clinically relevant phenotypic groups. The γ-globin gene promoter polymorphisms [− 158 C → T, + 25 G → A],BCL11A rs1427407 G → T, − 3 bp HBS1L-MYB rs66650371 and rs9399137 T → C polymorphisms were correlated with higher HbF, … lower disease severity score (P < .00001), milder clinical presentation, and a significant delay in the age [at receipt of the] first transfusion." The authors concluded that genetic interactions underlying the disease phenotype in this setting may be prognostic for clinical severity and useful in disease management.