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dc.contributor.authorda Rocha, Jorge E B
dc.contributor.authorOthman, Houcemeddine
dc.contributor.authorBotha, Gerrit
dc.contributor.authorCottino, Laura
dc.contributor.authorTwesigomwe, David
dc.contributor.authorAhmed, Samah
dc.contributor.authorDrögemöller, Britt I
dc.contributor.authorFadlelmola, Faisal M
dc.contributor.authorMachanick, Philip
dc.contributor.authorMbiyavanga, Mamana
dc.contributor.authorPanji, Sumir
dc.contributor.authorWright, Galen E B
dc.contributor.authorAdebamowo, Clement
dc.contributor.authorMatshaba, Mogomotsi
dc.contributor.authorRamsay, Michéle
dc.contributor.authorSimo, Gustave
dc.contributor.authorSimuunza, Martin C
dc.contributor.authorTiemessen, Caroline T
dc.contributor.authorBaldwin, Sandra
dc.contributor.authorChiano, Mathias
dc.contributor.authorCox, Charles
dc.contributor.authorGross, Annette S
dc.contributor.authorThomas, Pamela
dc.contributor.authorGamo, Francisco-Javier
dc.contributor.authorHazelhurst, Scott
dc.date.accessioned2021-11-03T18:35:13Z
dc.date.available2021-11-03T18:35:13Z
dc.date.issued2021-04-28
dc.identifier.urihttp://hdl.handle.net/10713/17052
dc.description.abstractIntroduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied-which has implications for drug safety and effective use in Africa. Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations. Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.en_US
dc.description.urihttps://doi.org/10.3389/fphar.2021.634016en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Pharmacologyen_US
dc.rightsCopyright © 2021 da Rocha, Othman, Botha, Cottino, Twesigomwe, Ahmed, Drögemöller, Fadlelmola, Machanick, Mbiyavanga, Panji, Wright, Adebamowo, Matshaba, Ramsay, Simo, Simuunza, Tiemessen, Baldwin, Chiano, Cox, Gross, Thomas, Gamo and Hazelhurst.en_US
dc.subjectADMEen_US
dc.subjectAfricaen_US
dc.subjectCNVen_US
dc.subjectgenetic diversityen_US
dc.subjectpharmacogenomicsen_US
dc.titleThe Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populationsen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fphar.2021.634016
dc.identifier.pmid34721006
dc.source.volume12
dc.source.beginpage634016
dc.source.endpage
dc.source.countrySwitzerland


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