Characterization of POR haplotype distribution in African populations and comparison with other global populations: Supplementary tables

Background & aim: POR is an enzyme that mediates electron transfer to enable the drug-metabolizing activity of CYP450 proteins. However, POR has been understudied in pharmacogenomics despite this vital role. The authors aimed to characterize the genetic variation in POR across African populations and to compare the star allele (haplotype) distribution with that in other global populations. Materials & methods: POR star alleles were called from whole-genome sequencing data using the StellarPGx pipeline. Results: In addition to the common POR*1 and *28 haplotypes (defined by rs1057868), five novel rare haplotypes were computationally inferred. No significant frequency differences were observed among the majority of African populations. However, POR*28 was observed at a higher frequency in individuals of non-African ancestry. Conclusion: This study highlights the distribution of POR alleles in Africa and across global populations with a view toward informing future precision medicine implementation.</p

Characterization of Novel CYP2D6 Alleles across Sub-Saharan African Populations

The CYP2D6 gene has been widely studied to characterize variants and/or star alleles, which account for a significant portion of variability in drug responses observed within and between populations. However, African populations remain under-represented in these studies. The increasing availability of high coverage genomes from African populations has provided the opportunity to fill this knowledge gap. In this study, we characterized computationally predicted novel CYP2D6 star alleles in 30 African subjects for whom DNA samples were available from the Coriell Institute. CYP2D6 genotyping and resequencing was performed using a variety of commercially available and laboratory-developed tests in a collaborative effort involving three laboratories. Fourteen novel CYP2D6 alleles and multiple novel suballeles were identified. This work adds to the growing catalogue of validated African ancestry CYP2D6 allelic variation in pharmacogenomic databases, thus laying the foundation for future functional studies and improving the accuracy of CYP2D6 genotyping, phenotype prediction, and the refinement of clinical pharmacogenomic implementation guidelines in African and global settings