Abstract

High levels of hemoglobin F (HbF) could reduce the severity of sickle cell disease (SCD) by inhibiting hemoglobin S (HbS) polymerization. HbF expression is modulated by the Quantitative Trait Loci (QTLs) located on the HBS1L-MYB intergenic region (HMIP) (rs28384513) and intron 2 of the B-cell lymphoma/leukemia 11A (BCL11A) gene (rs4671393, rs1427407). To assess the impact of QTLs of HbF on clinical and biological parameters associated with the severity of sickle cell disease in a Senegalese pediatric population, 301 children with SCD not treated with hydroxyurea were recruited. The numbers of hospitalizations and VOC were estimated over 2 years. HbF levels were determined by HPLC. Three QTLs of HbF were genotyped by High Resolution Melting (HRM), two single nucleotide polymorphisms (SNPs) of BCL11A and one SNP of HMIP. Data analysis was performed using SPSS. The mean frequency of hospitalizations was 0.84 ± 1.29. The mean number of vaso-occlusive crises (VOC) episodes was 2.73 ± 1.98. The mean Hb concentration was 7.76 ± 1.05 g/dl. The mean HbS was 82.28 ± 4.78% and the mean HbF was 9.49 ± 5.12%. BCL11A (rs1427407) was associated with fewer hospitalizations. Both BCL11A SNPs were associated with increased HbF levels. BCL11A SNPs were associated with increased HbF levels, decreased HbS levels, and decreased hospitalizations (rs1427407). However, no association was noted between these SNPs and the number of VOC episodes. Thus, HbF QTLs are not the only genetic factors modulating the clinical severity of sickle cell disease, which suggests the involvement of other genetic factors such as alpha-thalassemia.

Key words: sickle cell disease, hemoglobin F, quantitative trait loci of HbF, HBS1L-MYB intergenic region, B-cell lymphoma/leukemia, vaso-occlusive crises.