Human leukocyte antigen distribution and genomic ancestry in Brazilian patients with sickle cell disease

Hematopoietic stem-cell transplantation (HSCT) is currently the only established curative treatment for sickle cell disease (SCD), but is limited by donor availability. Ethnicity is thought to have an impact on the complications experienced by patients that undergo HSCT and on the likelihood of identifying an human leukocyte antigen (HLA) matched donor. In the present study, we investigated the genomic ancestry and the distribution of HLA allele groups in Brazilian patients with SCD, compared these HLA profiles to worldwide populations and evaluate the availability of HLA-matched donors. A broad intercontinental admixture of patients with SCD was observed, with African ancestry ranging from 6.7% to 93.4%. In a dendrogram based on HLA frequencies, Brazilian patients with SCD were included in a branch containing only populations with a significant African component. Among the 126 patients evaluated, 10 (8%) found a HLA-matched unrelated donor in a database of 18 134 donors. Self-reported white, brown and black matched donors were identified, and no significant difference in the percentage of compatible donors was observed between these ethnic groups. Our results show that Brazilian patients with SCD are very admixed, indicating that this group is a promising target for admixture mapping of genes involved in complications after HSCT. Additional studies may help to clarify the impact of the genetic diversity and admixture of these patients on the donor availability.