Raised Haemoglobin F (HbF) Level in Haemoglobinopathies: an Indicator of Polymorphism

Hemoglobinopathies are the most commonly encountered monogenic disorders of blood posing a major genetic and public health problem in Southeast Asia and the Indian subcontinent. Of the several abnormal hemoglobins so far identified, there are three variants sickle cell (Hb S), hemoglobin E (Hb E) and hemoglobin D (Hb D), which are predominantly prevalent in India. Among these clinically important hemoglobinopathies, hemoglobin E (Hb E) is mostly restricted to the North eastern states of India with high gene frequency. Hb E disorders may be found in heterozygous (AE), homozygous (EE) and compound heterozygous states (e. g. , Hb E with other abnormal hemoglobins or thalassemias) with widely variable clinical phenotypes. Studies suggest that there is a positive correlation of the E-globin gene with malaria endemicity. Since northeast India is a holoendemic area for Plasmodium falciparum and other types of malaria, it is reasonable to suspect that malaria might be acting as a selective factor for this gene. Increased levels of fetal hemoglobin (HbF, 22) are of no consequence in healthy adults, but confer major clinical benefits in patients with sickle cell anemia (SCA) and thalassemia, diseases that represent major public health problem. Higher level of Hb F is also associated with Hb E. The most significant genetic factor associated with high HbF is Xmn I polymorphism located at 158 upstream to the G globin genes. Thus Hb E, a haemoglobin variant which is clinically not very severe and associated with Xmn I polymorphism may be protective against malaria via production of high Hb F level.