Characterisation of novel CYP2D6 alleles across sub-Saharan African populations

The primary aim of this study was to characterize novel CYP2D6 star alleles found in sub-Saharan African populations, addressing the gap in pharmacogenetic data for these populations. The CYP2D6 gene is highly polymorphic and responsible for metabolising over 20% of medications in clinical use, making it a crucial gene in precision medicine. Despite this, African populations have been historically underrepresented in pharmacogenetic studies, and existing allele catalogues lack comprehensive data for African ancestry alleles.

The study utilised a variety of genotyping methods, including TaqMan-based assays, XL-PCR, and nanopore sequencing to characterise CYP2D6 alleles in 30 individuals from sub-Saharan African populations. Nanopore sequencing was used to confirm copy number variants (CNVs) and structural variations that are particularly common in CYP2D6. This helped the researchers resolve complex alleles and confirm previously uncharacterised variants.

The major findings include the identification of 14 novel CYP2D6 star alleles, which were experimentally validated and added to the PharmVar database. These new alleles, such as CYP2D6 *146, *149, and CYP2D6 *152 to *163, are expected to enhance the accuracy of genotype-phenotype predictions for African populations. Many of these alleles were predicted to have altered or diminished function based on in silico tools, which has important implications for drug metabolism in individuals carrying these variants. The study underscores the need for more comprehensive pharmacogenetic studies in African populations to improve precision medicine globally.