P1475: THE ROLE OF BCL11A AND HBS1L-MYB SINGLE NUCLEOTIDE POLYMORPHISMS IN EGYPTIAN SICKLE CELL DISEASE PATIENTS

Abstract

Background: Sickle cell disease (SCD) is a debilitating blood disorder with a highly variable phenotype. Inter-individual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. The only currently FDA-approved HbF inducing drug for sickle cell disease (SCD) is hydroxyurea (HU). Genome wide association studies (GWAS) have identified three major quantitative trait loci (QTL) (intergenic region of HBS1L-MYB, BCL11A gene and XmnI site) associated with HbF. Several single nucleotide polymorphisms (SNPs) with persistence of HbF and amelioration of disease severity of β-thalassemia (β-thal) and SCD have been identified. Aims: The aim of the current study is to find the influence of these genetic modifiers, especially BCL11A (rs4671393) and HBS1L-MYB intergenic region (rs9399137) SNPs on the level of HbF, severity of SCD and response to hydroxyurea in Egyptian sickle cell disease patients. Methods: The present study included 100 patients with SCD; 56 patients were diagnosed as homozygous sickle cell anemia (SS) patients, while 44 patients were diagnosed as sickle beta thalassemia patients (Sβ). Genotyping for the genes was done by Real-Time PCR (RT-PCR) technique. Results: BCL11A (rs4671393) SNP showed higher hemoglobin and HbF levels when induced with HU, with significantly higher increment in HbF level post HU therapy as well as a milder clinical phenotype in our Sβ patients’ group. In our SS patients’ group it showed a lower incidence of pneumonia as well as a more effective response to HU treatment. HBS1L-MYB intergenic region (rs9399137) SNPs showed lower reticulocytic counts and serum ferritin levels in our Sβ patients’ group. Summary/Conclusion: In conclusion, our study shows that BCL11A (rs4671393) SNP showed higher hemoglobin and HbF levels when induced with HU, with significantly higher increment in HbF level post HU therapy as well as a milder clinical phenotype in our Egyptian study.