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

Abstract

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.

Keywords: Africa; CYP450; Drug development; Drug metabolism; Genetic diversity; Pharmacogenetics.

Fig. 1

Flow diagram of study selection.

Fig. 2

Pharmacogenetics PCA cluster of global populations according to different CYP allele frequencies. PCA analysis identifies X-variables (CYP variants) that most differentiate Y-objects (African/Asian/Caucasian populations). In this analysis, the software projects the populations into clusters based on shared characteristics with respect to the frequency and/or absence of the CYP variants analyzed. Green ovals indicate African populations. Blue ovals indicate Caucasian populations. Red ovals indicate Asian populations. Kikuyu, Luo and Maasai are regional populations of Kenya. Hausa, Igbo and Yoruba are regional populations of Nigeria. San and Shona are regional populations of Zimbabwe. Xhosa is a regional population of South Africa. CYP, cytochrome P450; PCA, principal components analysis.