Closed relationship of βE-allele and high HbF associated cis-loci: Case studies in Thai HbE/ β-thalassemia families

Abstract

Introduction :  Previous statistical analyses have demonstrated linkage disequilibrium of β^E-allele and surrounding in-cis sequences.

Objective : To confirm the linkage disequilibrium of β^E-allele and surrounding in-cis sequences.

Materials and Methods : Associations of the β^E-allele with the β-globin haplotype, (AT)_xN_z(AT)_y motif of βLCR-HS2, XmnI-^Gg polymorphism, pre-^Gg framework, (TG)n motif in IVSII of  ^Ag-globin gene and HBBP1 : rs2071348 polymorphism were analyzed in three Thai HbE/β^O-thalassemia families.

Results : The β^E-allele was always in-cis with the β-globin haplotype III, pre ^Gg-framework 2, XmnI+, (TG)₁₃ motif within IVSII of  ^Ag- globin gene and “C” at HBBP1 : rs2071348 locus, all previously shown to be associated with high HbF expression. Combination of the (AT)₉N₁₂(AT)₁₀ motif of βLCR-HS2 and these cis-acting factors seemed to be required for maximum HbF-expression.

Conclusion : This family study substantially confirmed the linkage between the β^E allele and cis-acting loci associated with high HbF phenotype. This study also highlighted the closed relationship between HbE and HbF as well as the need of combination of the analyzed cis-acting sequences in activating HbF expression in human. 

Bull Chiang Mai Assoc Med Sci 2015; 48(2): 88-99. Doi: 10.14456/jams.2015.14