Existence of HbF Enhancer Haplotypes atHBS1L-MYBIntergenic Region in Transfusion-Dependent Saudiβ-Thalassemia Patients

Abstract

Background and Objectives.β-Thalassemia and sickle cell disease are genetic disorders characterized by reduced and abnormalβ-globin chain production, respectively. The elevation of fetal hemoglobin (HbF) can ameliorate the severity of these disorders. In sickle cell disease patients, the HbF level elevation is associated with three quantitative trait loci (QTLs),BCL11A,HBG2 promoter, andHBS1L-MYBintergenic region. This study elucidates the existence of the variants in these three QTLs to determine their association with HbF levels of transfusion-dependent Saudiβ-thalassemia patients.Materials and Methods. A total of 174 transfusion-dependentβ-thalassemia patients and 164 healthy controls from Eastern Province of Saudi Arabia were genotyped for fourteen single nucleotide polymorphisms (SNPs) from the three QTL regions using TaqMan assay on real-time PCR.Results. Genotype analysis revealed that six alleles ofHBS1L-MYBQTL (rs9376090Cp=0.0009, rs9399137Cp=0.008, rs4895441Gp=0.004, rs9389269Cp=0.008, rs9402686Ap=0.008, and rs9494142Cp=0.002) were predominantly associated withβ-thalassemia. In addition, haplotype analysis revealed that haplotypes ofHBS1L-MYB(GCCGCACp=0.022) andHBG2 (GTTp=0.009) were also predominantly associated withβ-thalassemia. Furthermore, theHBS1L-MYBregion also exhibited association with the high HbF cohort.Conclusion. The stimulation of HbF gene expression may provide alternative therapies for the amelioration of the disease severity ofβ-thalassemia.