title: Klf10 Gene, a Secondary Modifier and a Pharmacogenomic Biomarker of Hydroxyurea Treatment Among Patients With Hemoglobinopathies.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: *Thalassemia Center †Molecular Genetics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mohsen S
authors.initials: MS
authors.lastname: Elalfy
authors.forename: Nayera H K
authors.initials: NH
authors.lastname: El Sherif
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Kamal
authors.forename: Nihal H
authors.initials: NH
authors.lastname: Aly
mesh_terms: D002648:Child; D003430:Cross-Sectional Studies; D051765:Early Growth Response Transcription Factors / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000032:analysis; D060045:Genes, Modifier; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D006453:Hemoglobinopathies / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: D051765:Early Growth Response Transcription Factors; D005819:Genetic Markers; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D005319:Fetal Hemoglobin; D006918:Hydroxyurea