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.