Fetal‐haemoglobin enhancing genotype at BCL11A reduces HbA 2 levels in patients with sickle cell anaemia

Abstract

Understanding the interplay of genetic factors with haemoglobin expression and pathological processes in sickle cell disease is important for pharmacological and gene‐therapeutic interventions. In our nascent study cohort of Nigerian patients, we found that three major disease‐modifying factors, HbF levels, α‐thalassaemia deletion and BCL11A genotype, had expected beneficial haematological effects. A key BCL11A variant, while improving HbF levels (5.7%–9.0%), also led to a small, but significant decrease in HbA 2 . We conclude that in general, interventions boosting HbF are likely to reduce HbA 2 in patients’ erythroid cells and that such therapeutic strategies might benefit from a parallel stimulation of HbA 2 through independent mechanisms.