Background: The klf10 gene could indirectly modify γ-globin chain production and hence the level of fetal hemoglobin (HbF) ameliorating the phenotype of β-hemoglobinopathies and the response to hydroxycarbamide (hydroxyurea [HU]) therapy. In this study, we aimed to evaluate the frequency of different genotypes for the klf10 gene in β-thalassemia major (B-TM), β-thalassemia intermedia (B-TI), and sickle cell disease (SCD) patients by polymerase chain reaction and to assess its relation to disease phenotypes and HU response.
Methods: This cross-sectional study included 75 patients: 50 B-TM, 12 SCD, and 13 B-TI patients (on stable HU dose). The relation of the klf10 gene polymorphism (TIEG, TIEG1, EGRα) (rs3191333: c*0.141C>T) to phenotype was studied through baseline mean corpuscular volume, HbF, and transfusion history, whereas evaluation of response to HU therapy was carried out clinically and laboratory.
Results: The frequency of the mutant klf10 genotype (TT) and that of the mutant allele (T) was significantly higher among B-TM patients compared with those with B-TI and SCD patients. Only homozygous SCD patients for the wild-type allele within the klf10 gene had a significantly lower transfusion frequency. The percentage of HU responders and nonresponders between different klf10 polymorphic genotypes among B-TI or SCD patients was comparable.
Conclusions: Although the klf10 gene does not play a standalone role as an HbF modifier, our data support its importance in ameliorating phenotype among β-hemoglobinopathies.