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 βE-allele and surrounding in-cis sequences. Objective : To confirm the linkage disequilibrium of βE-allele and surrounding in-cis sequences. Materials and Methods : Associations of the βE-allele with the β-globin haplotype, (AT)xNz(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/βO-thalassemia families. Results : The βE-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 βE 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

Keywords

• HbE/βO-thalassemia
• HbF
• β-globin haplotype
• β-globin mutations
• cis-acting loci