Journal
EBIOMEDICINE
Volume 17, Issue -, Pages 67-74Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.02.017
Keywords
Pharmacogenetics; CYP450; Genetic diversity; Drug metabolism; Africa; Drug development
Funding
- Novartis Pharma AG
- Novartis Pharma AG
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Genetic diversity is greater in Africa than in other continental populations. Genetic variability in genes encoding drug metabolizing enzymesmay 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 distributionswe 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. (C) 2017 The Authors. Published by Elsevier B.V.
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