Relationship between DNA polymorphisms at the BCL11A and HBS1L-MYB loci in beta-Thalassemia patients with increased fetal hemoglobin levels

ABSTRACT

High fetal hemoglobin [HbF] levels have a major impact on the hemoglobin disorders, i.e. beta -Thalassemia. Increased HbF production ameliorates the disease severity. Three loci-HBS1L-MYB intergenic region on chromosome 6q23, BCL11A on chromosome 2pl6, and the chi-globin gene on chromosome 11 account for up to 50% of the variations in HbF levels in patients with sickle cell anemia, thalassemia and healthy adults. In the present study, we evaluated the relationship between some polymorphisms on HBS1L-MYB BCL11A loci and increased HbF levels in thalassemia patients and normal subjects. In this case-control study, three common polymorphisms among 50 beta-thalassemia patients with increased HbF and 47 healthy individuals with normal HbF by using PCR-RFLP were genotyped rs4895441, rsl 1886868, and rs28384513. Enzymatic digestion was performed by Rsal, MboII, and BstXI, respectively. Correlations with high levels of HbF were performed with a Chi-square test by using SPSS 16 and SNP analyzer2. Mutant allelic frequencies were 0.245, 0.521 and 0.309 in healthy and 0.3, 0.52 and 0.28 in patient for rs4895441, rsl 1886868 and rs28384513, respectively. Significant relationship was not observed among three polymorphisms studied in healthy volunteers and beta-Thalassemia major patients with increased HbF levels and P-value allelic and genotypic was higher than 0.05 at three SNPs. In spite of previous reports, evaluation of polymorphisms at the BCL11A and HBS1L-MYB loci in this study did not show up a significant correlation with increased HbF. Other polymorphisms might have a role in increasing HbF in our population