African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development

Genetic diversity is greater in Africa than in other continental populations. Genetic variability in genes encoding drug metabolizing enzymes may contribute to the high numbers of adverse drug reactions reported in Africa. We reviewed publications (1995–April 2016) reporting frequencies of known cytochrome P450 (CYP) variants in African populations. Using principal components analysis (PCA) we identified CYP alleles of potential clinical relevance with a marked difference in distribution in Africa, compared with Asian and Caucasian populations. These were CYP2B6*6, CYP2C8*2, CYP2D6*3, CYP2D6*17, CYP2D6*29, CYP3A5*6, and CYP3A5*7. We show clearly that there is greater diversity in CYP distribution in Africa than in other continental populations and identify a need for optimization of drug therapy and drug development there. Further pharmacogenetic studies are required to confirm the CYP distributions we identified using PCA, to discover uniquely African alleles and to identify populations at a potentially increased risk of drug-induced adverse events or drug inefficacy.
Highlights • Greater diversity in CYP450 distribution in Africa vs Europe or Asia was demonstrated. • CYP alleles with a marked difference in distribution in Africa were identified. • CYP alleles that may be uniquely African were highlighted. • These data may help to identify regions at a greater risk of adverse drug reactions. Genetic diversity is greater in Africa than in other populations, yet in clinical therapeutics and drug development Africa is often treated as a homogenous, single entity. Genetic diversity in cytochrome P450 (CYP) genes may contribute to high numbers of adverse drug reactions reported in Africa. Reports on polymorphisms in drug metabolizing enzymes in African populations are limited. Our study demonstrates greater genetic diversity in CYPs in Africa and identifies CYP alleles with markedly different distribution in Africa compared with other populations. Our data can help identify African regions at potentially greater risk of adverse drug reactions or drug inefficacy.