Distribution of Pharmacogenetic Polymorphisms in Ethiopians: A Systematic Review and Meta-analysis

Aim: Pharmacogenetic variant frequencies vary substantially across ancestral populations, yet African populations remain understudied. This systematic review aimed to characterize the distribution of pharmacogenetic variants among Ethiopians. Methods: Following the PRISMA guidelines, a literature search was performed across PubMed, Web of Science, Embase, Scopus, and Cochrane Central Register of Controlled Trials. Random-effects meta-analyses were performed to estimate pooled allele, genotype, and genotype-predicted phenotype frequencies. Results: A total of 73 studies were included, involving Ethiopian participants from diverse study populations. Overall, 37 pharmacogenes were investigated, predominantly drug-metabolizing enzymes. Pooling and meta-analyses revealed substantial frequencies of clinically relevant decreased-, increased- and no-function alleles. The no-function CYP3A5*3 allele and decreased-function CYP2B6*6 occurred at a frequency of 62% and 31%, respectively. Decreased-function CYP2C9 alleles (*2 and *3) were observed at lower frequencies (<5%). For CYP2D6, both decreased-function alleles (*41: 21%; *17: 12%), and gene duplications (*1xN and/or *2xN: 14%) were common. The frequencies of no-function CYP2C19*2 and increased-function CYP2C19*17 alleles were 13% and 18%, respectively. The no-function SLCO1B1 c.521T>C variant occurred at a frequency of 19%. Ethnicity substantially contributed to the observed heterogeneity in CYP3A5, CYP3A4, CYP2C9, CYP2C19 and TPMT allele frequencies. Conclusion: These findings provide comprehensive evidence on the distribution and clinical relevance of pharmacogenetic variants in Ethiopians, providing an important foundation for future pharmacogenomics research and implementation. The findings also underscore the need for greater inclusion of African populations in precision medicine research to ensure that genomic medicine is informed by population-specific evidence.