ß-Globin gene cluster haplotypes in Moroccan sickle cell disease patients: diversity pilot study

Sickle cell disease (SCD) is the most common inherited blood disorder worldwide. Although monogenic, it presents substantial clinical heterogeneity influenced by genetic modifiers, including haplotypes and fetal hemoglobin (HbF) levels.

This pilot cross-sectional study aimed to characterize, for the first time, the βS gene haplotype distribution among Moroccan patients with sickle cell anemia and evaluate its impact on hematological parameters, particularly HbF levels.

Eight polymorphic sites within the β-globin gene cluster were analyzed using PCR-RFLP in 334 chromosomes from SCD patients in northern Morocco. Associations between haplotypes and HbF levels were evaluated.

PCR RFLP showed that the Benin haplotype was the most common (61.1%), followed by Bantu (14.1%), Atypical A1 (11.7%), Senegal (10.5%), and Arab-Indian (2.7%). The most frequent genotypes were Ben/Ben (41.3%), Ben/CAR (15%), and Ben/Sen (10.2%). HbF levels varied significantly across haplotypes (p < 0.005), with Senegal and Arab-Indian showing the highest levels and Benin and Bantu the lowest.

This study highlights both the genetic and anthropological diversity of SCD in Morocco, likely reflecting historical African gene flow. Haplotype profiling enhances understanding of genotype-phenotype correlations, offering valuable insights for prognosis and individualized care strategies to improve patients' outcomes.