Significance of Genetic Modifiers of Hemoglobinopathies Leading Towards Precision Medicine

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.

Scientific Reports (Nature)