Foetal haemoglobin in normal healthy adults: relationship with polymorphic sequences cis to the beta globin gene

We evaluated the effects of polymorphic markers within the beta globin gene cluster on HbF expression in two groups. These groups were randomly selected from a survey of HbF distribution in a large population study of unrelated healthy Algerian adults (n=827). The first group contained individuals with normal HbF levels (0.1-0.5%) and the second group contained individuals with raised HbF levels (0.8-2.3%). Of the various polymorphic markers analysed, only the -309 G gamma A-->G, the -158 G gamma C-->T, the G gamma IVS2 TC (TG)(9) AG (TG)(2) (CG)(2) and the -540 beta (AT)(9) T(5) sequence configurations were significantly associated with increased HbF levels. More than 84% of the subjects with elevated HbF levels carried one or several of these four marker configurations, suggesting that the beta globin gene cluster exerts a significant effect on HbF expression in healthy individuals.