title: 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.
authors.affiliation: Department of Genetic Research, Institute for Research and Medical Consultation, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Cyril
authors.identifier: 0000-0001-7333-6486
authors.initials: C
authors.lastname: Cyrus
authors.affiliation: Department of Genetic Research, Institute for Research and Medical Consultation, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Chittibabu
authors.initials: C
authors.lastname: Vatte
authors.affiliation: Department of Genetic Research, Institute for Research and Medical Consultation, University of Dammam, Dammam, Saudi Arabia.
authors.forename: J Francis
authors.initials: JF
authors.lastname: Borgio
authors.affiliation: King Fahd Hospital of the University, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Rubaish
authors.affiliation: Department of Genetic Research, Institute for Research and Medical Consultation, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Shahanas
authors.identifier: 0000-0001-5037-4519
authors.initials: S
authors.lastname: Chathoth
authors.affiliation: Maternity and Children's Hospital, Dammam, Saudi Arabia.
authors.forename: Zaki A
authors.initials: ZA
authors.lastname: Nasserullah
authors.affiliation: Maternity and Children's Hospital, Dammam, Saudi Arabia.
authors.forename: Sana Al
authors.initials: SA
authors.lastname: Jarrash
authors.affiliation: Al-Omran Scientific Chair for Hematological Diseases, King Faisal University, Maternity and Children's Hospital, Dammam, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sulaiman
authors.affiliation: Al-Omran Scientific Chair for Hematological Diseases, King Faisal University, Maternity and Children's Hospital, Dammam, Saudi Arabia.
authors.forename: Hatem
authors.initials: H
authors.lastname: Qutub
authors.affiliation: King Fahd Hospital of the University, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Hassan
authors.initials: H
authors.lastname: Alsaleem
authors.affiliation: College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Alhusain J
authors.initials: AJ
authors.lastname: Alzahrani
authors.affiliation: Center of Excellence in Sickle Cell Disease, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.affiliation: King Fahd Hospital of the University, University of Dammam, Dammam, Saudi Arabia; Al-Omran Scientific Chair for Hematological Diseases, King Faisal University, Maternity and Children's Hospital, Dammam, Saudi Arabia.
authors.forename: Amein K Al
authors.identifier: 0000-0003-2117-0669
authors.initials: AK
authors.lastname: Ali
mesh_terms: D000293:Adolescent; D001803:Blood Transfusion; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D021901:DNA, Intergenic / Q000235:genetics*; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012529:Saudi Arabia; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D021901:DNA, Intergenic; D005319:Fetal Hemoglobin