A Glimpse into Pharmacogenomics in Africa

Dandara, Collet; Matimba, Alice

doi:10.1017/9781139680295.007

The Genetics of African Populations in Health and Disease 2019

DOI: 10.1017/9781139680295.007

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A Glimpse into Pharmacogenomics in Africa

Collet Dandara¹,

Alice Matimba²

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Cited by 3 publications

(7 citation statements)

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“…It combines pharmacological and genomics principles, to predict effectiveness and safety of therapeutic agents. This is, in part, because drug response and toxicity are influenced by pharmacokinetic factors that result in interindividual variability in drug-metabolizing enzymes and membrane transporters [1]. Variants of relevance include members of the cytochrome P450 (CYP450) family.…”

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confidence: 99%

“…Pharmacogenomics research in Africa is especially valuable in the context of high genetic variability [1,3], high HIV burden and growing noncommunicable disease incidence. A recent publication on whole genome sequencing in hundreds of people from across Africa revealed an unexpectedly large number of new single-nucleotide variants [4].…”

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confidence: 99%

“…Moreover, genetic characteristics that influence PK and PD of drugs are poorly understood in African populations, thereby limiting treatment optimization [7]. Identified gene variants are useful for screening HIV-infected patients prior to treatment [1,2]. Likewise, study of additional pharmacogenomic parameters, such as clinical response to treatment or the ability to predict treatment failure, need to be carried out.…”

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confidence: 99%

“…There is a need to identify variants of pharmacogenomic relevance, within African populations [6]. This is crucial as the current evidence shows that not all identified genetic variants are applicable to the majority of African populations [1,5]. Hence, pharmacogenomic research is needed to provide robust clinical evidence, aid in drug development and for identifying genetic variants specific to highly diverse African populations.…”

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confidence: 99%

“…Few have explored the role of genetic diversity on drug metabolism and treatment outcomes, in African populations. Yet, Africa is the epicenter of HIV and African populations exhibit greater genetic diversity than other world populations [1,9,17]. It is indeed, opportune time for pharmacogenomic studies to determine genes that can be used to screen patients in real-life HIV patient cohorts in Africa.…”

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Emerging Role for Pharmacogenomics in HIV Research in Africa

et al. 2021

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Emerging Role for Pharmacogenomics in HIV Research in Africa

et al. 2021

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The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review

Marwa¹,

Kapesa²,

Kamugisha³

et al. 2023

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Background Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations. Methods Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies. Results Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles. Conclusion This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among P. falciparum malaria patients.

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The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations

et al. 2021

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Introduction: 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.

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A Glimpse into Pharmacogenomics in Africa

Cited by 3 publications

References 176 publications

Emerging Role for Pharmacogenomics in HIV Research in Africa

Emerging Role for Pharmacogenomics in HIV Research in Africa

The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review

The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations

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