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Implications of African allele frequency variation in CYP450 genes for drug safety, efficacy and the future of drug development

Morgan, Thomas and Rajman, Iris (2017) Implications of African allele frequency variation in CYP450 genes for drug safety, efficacy and the future of drug development. EBioMedicine.. ISSN 2352-3964

Abstract

Genetic diversity is greater in Africa than in other continental populations. Genetic variability in genes encoding drug metabolising 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*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 optimisation of drug therapy and drug development there. Further pharmacogenetic studies are required to confirm the CYP distributions identified here, to identify uniquely African alleles and to identify populations at a potentially increased risk of drug-induced adverse events or drug inefficacy.

Item Type: Article
Date Deposited: 03 Mar 2017 00:45
Last Modified: 03 Mar 2017 00:45
URI: https://oak.novartis.com/id/eprint/31580

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