Effect of a group of genetic markers around the 5′ regulatory regions of the β globin gene cluster linked to high HbF on the clinical severity of β thalassemia

The clinical and hematological course of β thalassemia intermedia is influenced by a number of genetic factors which play a role in increasing fetal haemoglobin levels. Several polymorphisms located in the promoters of β and γ globin gene are involved in influencing the disease severity. Our objective was to study the effect of cis-DNA haplotypes, motifs, or polymorphisms (Pre G γ globin gene haplotypes, Aγ–δ intergenic region haplotypes XmnI and (AT)x(T)y polymorphisms, β-LCR HS2 and HS3 site motifs) that may contribute to higher HbF levels and a milder clinical course. We found that a combination of T haplotype of the Aγ–δ intergenic region, TAG Pre-Gγ haplotype, presence of the XmnI polymorphism along with the (AT)9(T)5 motif constitutes a topography that co-relates with raised HbF levels which may contribute in ameliorating the disease severity.