title: rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients.
abstract: OBJECTIVE
  Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia (SCA) by inhibiting deoxy sickle hemoglobin (HbS) polymerization. HbF genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Herein, we aimed to determine whether two functional polymorphisms of BCL11A are implicated in the variation of HbF and clinical events in SCA Tunisian patients.
  
  
  METHODS
  The studied population consisted of 148 SCA patients with SS phenotype. The group of patients was divided into two subgroups according to the threshold point of %HbF which is 15%. Genotyping of rs11886868 and rs4671393 was performed using PCR/Sequencing. To test for trait association with the candidate SNPs, genotype and allele frequencies between 'group who had %HbF < 15' and 'group who had %HbF >15' (controls) were compared using Pearson's chi-square test (compare 2, version 1.02). The association of each genotype and the combined genotype with complications was performed by logistic regression test.
  
  
  RESULTS
  Our findings showed that the majority of patients carried genotype CT of rs11886868 and genotypes AG and GG of rs4671393 present HbF level < 15%. RR = 0.08, RR = 0.176, and RR = 0.189, respectively. The results showed a significant association between the alleles T of rs11886868 and G of rs4671393 and %HbF < 15% with P = 0.016; RR = 0.39 and P = 8.9 × 10(-3): RR = 0.567, respectively. Interestingly, the C allele of the rs11886868 and the A allele of the rs46713939 were associated with an ameliorated phenotype in patient's SCA. The combination of the genotypes GG and CT explains more phenotypic variance than the sum of the two BCL11A SNPs taken individually.
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Chaouch
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Moumni
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Houyem
authors.initials: H
authors.lastname: Ouragini
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Darragi
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Miniar
authors.initials: M
authors.lastname: Kalai
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Dorra
authors.initials: D
authors.lastname: Chaouachi
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Boudrigua
authors.affiliation: b Université de Tunis El Manar, Hopital Aziza Othmena, d'Hématologie Clinique , Tunisia.
authors.forename: Raouf
authors.initials: R
authors.lastname: Hafsia
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunisia.
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins; D012189:Retrospective Studies
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin
keywords: BCL11A gene; HbF; Sickle cell anemia