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

Abstract

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.

HLA diversity in Brazil

“…This result may point to alleles that can be associated to this condition. The same is observed in the population composed by sickle cell anemia patients, which may reflect a higher African genetic background in these individuals.…”

“…A study with patients with sickle cell anemia in the state of Minas Gerais investigated genomic ancestry based on HLA variability. When comparing the HLA frequencies of this population with European, African and Native American populations, the Brazilian population of patients with sickle cell anemia in this study indicated a significant African component, in spite of significant admixture …”

“…When comparing the HLA frequencies of this population with European, African and Native American populations, the Brazilian population of patients with sickle cell anemia in this study indicated a significant African component, in spite of significant admixture. 63 Association studies between autoimmune diseases and HLA variants have been performed in Brazilian populations. In the state of Paraná, 86 patients with multiple sclerosis were investigated for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 frequencies, and the HLA-DQB1*02:03 allele was associated with the disease 55 (Table 2).…”

Probability of success in the search for a related bone marrow donor in Cologne, Germany using HLA‐A, ‐B and ‐DRB1 haplotype frequencies

“…Determinations could not be made in all cases. Another approach was to determine the ethnicity by using ancestry‐informative markers . This was not possible in all cases due to the fact that we analyzed empirical data with ambiguous typing resolution.…”

“…Another approach was to determine the ethnicity by using ancestry-informative markers. 10 This was not possible in all cases due to the fact that we analyzed empirical data with ambiguous typing resolution. In light of this and the small sample size compared with other publications, [11][12][13][14][15][16][17][18] these families were kept in the analysis.…”