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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 cyt...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360579/ https://www.ncbi.nlm.nih.gov/pubmed/28237373 http://dx.doi.org/10.1016/j.ebiom.2017.02.017 |
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author | Rajman, Iris Knapp, Laura Morgan, Thomas Masimirembwa, Collen |
author_facet | Rajman, Iris Knapp, Laura Morgan, Thomas Masimirembwa, Collen |
author_sort | Rajman, Iris |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5360579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-53605792017-03-30 African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development Rajman, Iris Knapp, Laura Morgan, Thomas Masimirembwa, Collen EBioMedicine Research Paper 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. Elsevier 2017-02-20 /pmc/articles/PMC5360579/ /pubmed/28237373 http://dx.doi.org/10.1016/j.ebiom.2017.02.017 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Rajman, Iris Knapp, Laura Morgan, Thomas Masimirembwa, Collen African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development |
title | African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development |
title_full | African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development |
title_fullStr | African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development |
title_full_unstemmed | African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development |
title_short | African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development |
title_sort | african genetic diversity: implications for cytochrome p450-mediated drug metabolism and drug development |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360579/ https://www.ncbi.nlm.nih.gov/pubmed/28237373 http://dx.doi.org/10.1016/j.ebiom.2017.02.017 |
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