DIVERSITY OF β-GLOBIN HAPLOTYPES IN SICKLE CELL DISEASE PATIENTS FROM BRAZIL

Abstract

The characterization of beta globin (β-Hbb) gene haplotypes in sickle cell anemia patients continues to be a valuable source of information for understanding the heterogeneity of the clinical manifestations of this disease and for the regional and global interpretation of human migrations. In this work, we performed the characterization of the main β-Hbb gene haplotypes in 327 sickle cell disease patients from the South, Midwest and Southeast of Brazil, applying a multiplex system of single nucleotide polymorphisms (SNP). In addition, a comparative historical investigation was carried out on the distribution of β-Hbb haplotypes in Brazil and in twelve Brazilian states. Our results revealed that the Central African Republic (CAR) or Bantu haplotype was the most common in the Southeast (68%), Midwest (64%) and South (74%) regions of Brazil, followed by Benin (BEN), found in 28%, 35% and 19% respectively. The distribution of genotypes revealed a predominance of CAR/CAR in the Southeast (51%) and South (58%) regions, but in the Midwest region, the most patients (44%) had BEN/CAR genotypes, followed by CAR/CAR (43%) and BEN/BEN (13%) genotypes. When we evaluated the scenario of the β-Hbb gene haplotypes distribution in Brazil, we found the most prevalent was CAR (65%) followed by Benin (28%). This result reflects the data found in the majority of the evaluated Brazilian states, except for Bahia, which showed a predominance of the Benin haplotype (47%). Indeed, it is important to emphasize that this result corresponds mainly to the South, Southeast and Northeast Brazilian regions and for the Midwest and North regions, studies still are scarce or non-existent. The historical analysis of the β-Hbb gene haplotypes distribution revealed an increasing trend (1.2-fold) in the percentage of individuals with CAR haplotype and a decrease of Benin over the years, except for Bahia and Rio Grande do Sul. Though, the interpretation of this result requires considerations related to the methodology used in the study, sample number and the region-specific population evaluated. However, the increasing number of CAR haplotype individuals is worrying, since this haplotype is associated with more severe clinical outcomes in sickle cell patients. In conclusion, understanding the β-Hbb gene haplotypes distribution in Brazil can contribute significantly to improvements in clinical management and therapeutic care in each region, including specific and personalized interventions to increase the survival of sickle cell patients. Funding: FAPESP2017/26950-6; FUNDERP.