Fetal Hemoglobin Levels and βsGlobin Haplotypes in an Indian Population With Sickle Cell Disease

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 βsglobin gene was found to be linked almost exclusively to a βshaplotype (+ ++ - + +—), which is also common in Saudi Arabian patients from the Eastern Province (referred to as the Asian β*haplotype). By contrast, the majority of βAand 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 homozy-gotes (SS). This factor appears to be related to the Asian βs 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.