title: Fetal Hemoglobin in Tunisian Sickle Cell Disease Patient: Relationship with Polymorphic Sequences Cis to the β-Globin Gene.
abstract: Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. We evaluated the effects of polymorphic markers within the β-globin gene cluster to identify the genetic mechanics that influence HbF on Tunisian sickling patients (n = 242). Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the framework polymorphism was established by PCR-sequencing, four independent regions of interest were identified: the 5' region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal (Gγ and Aγ) genes and the 5' region of β-globin gene. The correlation of these various Haplotypes and SNPs with HbF expression and clinical data was studied. Our data showed that among the various polymorphic markers analyzed, only the sequence (AT)xN12(AT)y in LCR HS2 region was significantly associated (p < 0.05) with increased HbF levels, suggesting that the β-globin gene cluster exerts a significant effect on HbF in sickle cell patients. This study can improve understanding of the physiopathology of the disease and aid to increase our ability to predict clinical severity.
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Imen
authors: I
authors: Moumni
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Maha
authors: M
authors: Ben Mustapha
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Ikbel
authors: I
authors: Ben Mansour
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Amine
authors: A
authors: Zoraï
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Kaïs
authors: K
authors: Douzi
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Sarah
authors: S
authors: Sassi
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Dorra
authors: D
authors: Chaouachi
authors: Service d'Immuno-Hématologie pédiatrique, Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia.
authors: Fethi
authors: F
authors: Mellouli
authors: Service d'Immuno-Hématologie pédiatrique, Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia.
authors: Mohamed
authors: M
authors: Bejaoui
authors: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors: Salem
authors: S
authors: Abbes
keywords: Fetal hemoglobin (HbF); Microsatellite repeats; Sickle cell anemia