Fetal hemoglobin levels and β(s) globin haplotypes in an Indian population with sickle cell disease

Abstract

To further explore the cause for variation in hemoglobin F (Hb F) levels in sickle cell disease, the β globin restriction-fragment length polymorphism haplotypes were determined in a total of 303 (126 SS, 141 AS, 17 Sβ°, 7 Aβ°, and 12 AA) Indians from the state of Orissa. The β(s) globin gene was found to be linked almost exclusively to a β(s) haplotype (+++-++-), which is also common in Saudi Arabian patients from the Eastern Province (referred to as the Asian β(s) haplotype). By contrast, the majority of β(A) and β° thalassemia globin genes are linked to haplotypes common in all European and Asian populations (+-----[+/-]; --++-++). Family studies showed that there is a genetic factor elevating Hb F levels dominantly in homozygotes (SS). This factor appears to be related to the Asian β(S) globin haplotype, and a mechanism for its action is discussed. There is also a high prevalence of an independent Swiss type hereditary persistence of fetal hemoglobin (HPFH) determinant active in both the sickle cell trait and in sickle cell disease.