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.