Pharmacogenomic diversity in Amazonian Indigenous populations: implications for Berlin–Frankfurt–Münster acute lymphoblastic leukemia therapy

Purpose This study aimed to characterize pharmacogenomic variation in genes involved in the metabolism and transport of drugs used in Berlin–Frankfurt–Münster-based therapy in Amazonian Indigenous individuals and to compare allele frequencies with major continental populations. Methods/patients Whole-exome sequencing data previously generated from 64 healthy Indigenous individuals from 12 Amazonian ethnic groups were analyzed. A total of 120 genes associated with drugs used in Berlin–Frankfurt–Münster protocols were selected. Variants were annotated and filtered using bioinformatic quality-control criteria, and allele frequencies were compared with African, Admixed American, East Asian, European, and South Asian populations from the 1000 Genomes Project. Multidimensional scaling was used to assess population-level genetic similarity. Results After quality control, 648 variants were identified. Twenty-eight variants were observed exclusively in the Indigenous study population, including four nonsynonymous coding variants with moderate predicted impact. Significant allele-frequency differences were observed for ADA rs11555566, CBR3 rs881711, and CYP2B6 rs3745274; rs881711 and rs3745274 differed from all five reference populations. Multidimensional scaling showed a distinct Indigenous pharmacogenomic profile, with greater similarity to the Admixed American population. Conclusions Amazonian Indigenous populations exhibit substantial pharmacogenomic diversity in genes relevant to Berlin–Frankfurt–Münster-based therapy. These findings identify candidate variants for functional and clinical validation and reinforce the importance of including underrepresented populations in pharmacogenomic research.