title: The influence of the BCL11A polymorphism on the phenotype of patients with beta thalassemia could be affected by the beta globin locus control region and/or the Xmn1-HBG2 genotypic background.
abstract: To study the influence of the β globin locus control region (LCR) genotypic background on the phenotype modifying role of BCL11A polymorphisms, 100 cases of thalassemia, 48 homozygous for the A allele and 52 homozygous for the G allele at the 5'HS4-LCR palindromic polymorphic site were genotyped for two BCL11A single nucleotide polymorphisms (rs11886868 and rs766432) in the intronic region of this gene. The effect of these polymorphisms on HbF variation was also examined in 122 normal individuals. The 5'HS4-LCR had the most significant role in determining the phenotype of these thalassemia patients. BCL11A polymorphisms showed a significant role in determining the phenotype of patients homozygous for the G allele at 5'HS4-LCR. However, the majority of patients homozygous for the A allele at 5'HS4-LCR, showed a severe phenotype, regardless of the BCL11A genotype. These results, without undermining the strength of BCL11A as a silencer of the γ globin gene, suggest that the LCR background, by governing the state of BCL11A binding to this region, plays a more significant role in determining the thalassemia phenotype than the level of BCL11A protein expression, that might be influenced by single nucleotide polymorphisms in intronic regions of the BCL11A gene. Functional studies to confirm the interactions between BCL11A and LCR could be useful in designing pharmacogenetic strategies for the treatment of beta thalassemia major.
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. nneisha@gmail.com
authors.forename: Maryam
authors.initials: M
authors.lastname: Neishabury
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Zamani
authors.forename: Elahe
authors.initials: E
authors.lastname: Keyhani
authors.forename: Azita
authors.initials: A
authors.lastname: Azarkeivan
authors.forename: Seyedeh Sedigheh
authors.initials: SS
authors.lastname: Abedini
authors.forename: Masumeh Sadat
authors.initials: MS
authors.lastname: Eslami
authors.forename: Setareh Talebi
authors.initials: ST
authors.lastname: Kakroodi
authors.forename: Mahjoobeh Jafari
authors.initials: MJ
authors.lastname: Vesiehsari
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
mesh_terms: D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D019901:Locus Control Region; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055544:beta-Globins; D005319:Fetal Hemoglobin