title: 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.
authors.affiliation: Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland. Electronic address: Iris.rajman@novartis.com.
authors.forename: Iris
authors.initials: I
authors.lastname: Rajman
authors.affiliation: PharmaGenesis London, London, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Knapp
authors.affiliation: Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Morgan
authors.affiliation: African Institute of Biomedical Science & Technology, Harare, Zimbabwe.
authors.forename: Collen
authors.initials: C
authors.lastname: Masimirembwa
mesh_terms: D000349:Africa; D044383:Black People / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D055808:Drug Discovery; D005787:Gene Frequency; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: D003577:Cytochrome P-450 Enzyme System
keywords: Africa; CYP450; Drug development; Drug metabolism; Genetic diversity; Pharmacogenetics