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Genomics Applications for the Developing World pp 161–182Cite as

Pharmacogenomics in Africa

Diversity as an Opportunity for Personalized Health Care

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Part of the book series: Advances in Microbial Ecology ((AMIE))

Abstract

The developed world has made significant advances in translating pharmacogenetics/genomics research into medical solutions that aim to personalize treatment that is based on a patients’ genetic status. Africa, on the other hand, has lagged behind in these advances, but recent developments are showing great potential for pharmacogenomics research and clinical applications on the continent. The genetic variability of African populations is proving an invaluable tool for understanding susceptibility and/or resistance to infectious diseases or noncommunicable diseases and the search for biomarkers for drug safety and efficacy. Studies on the polymorphism of genes that code for drug-metabolizing enzymes (CYP2B6, 2C9, 2C19, 2D6, FMO, NAT2, GSTT and GSTM) in nine major African ethnic groups (Yoruba, Ibo, Hausa, Kikuyu, Masaai, San, Luo, Venda, and Shona) showed genetic clustering of these populations distinct from that of Asian and of Caucasian populations. Clinical studies on the effect of the CYP2B6G516T variant on efavirenz concentrations were predictive of a dose reduction to a third of the standard dose in patient homozygous of the variant. This could have significant effects on the safe and efficacious use of this drug in Africa where 20% of the people are homozygous for this variant compared to about 5% in Caucasian and Oriental populations. We also found that CYP2C9 variants associated with dose optimization of warfarin in Caucasians are very rare in African populations. This has implication on the utility of commercial genetic diagnostic kits in use in Europe, which might not be applicable in African populations. Molecular evolution studies on the nine major ethnic groups and in comparison with data on Caucasian and Oriental populations using the Illumina chip with 600 K SNPs confirmed the genetic diversity of African populations and their distinct difference from other non-African populations. Though only a few genome-wide association studies (GWAS) have been done on common infectious diseases in Africa (malaria, TB, and HIV), interest in the scientific community to conduct such studies on noncommunicable disease in Africa will provide the scientific and technological impetus for genomic medicine research in Africa.

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Abbreviations

ACE:

Angiotensin Converting Enzyme

ADMET:

Absorption Distribution, Metabolism, Excretion, Toxicity

ADR:

Adverse Drug Reaction

AFSHG:

African Society of Human Genetics

AIBST:

African Institute of Biomedical Science and Technology

AIDS:

Acquired Immunodeficiency Syndrome

AMOVA:

Analysis of Molecular Variance

ART:

Anti-Retroviral Treatment

ARV:

Anti-Retroviral

CEPH:

Centre d’Etude du Polymorphisme Humain

CNS:

Central Nervous System

CNV:

Copy Number Variant

CYP:

Cytochrome P-450

DME:

Drug-Metabolizing Enzyme

FDA:

Food and Drug Administration

G6PD:

Glucose 6-Phoshate Dehydrogenase

GST:

Glutathione S-Transferase

GWAS:

Genome-Wide Association Study

H3 Africa:

Human Heredity and Health in Africa

HIV:

Human Immunodeficiency Virus

HLA:

Human Leukocyte Antigen

INR:

International Normalized Ratio

LD:

Linkage Disequilibrium

NAT:

N-actetyltransferase

NIH:

National Institutes of Health

OCT:

Organic Cation Transporter

P4:

Personalized Predictive, Preventive and Participatory

PD:

Pharmacodynamics

PK:

Pharmacokinetics

SNP:

Single Nucleotide Polymorphism

TB:

Tuberculosis

TPMT:

Thiopurine S-Methyl Transferase

VKOR:

Vitamin K Oxidoreductase

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Acknowledgments

The authors acknowledge funding from EDCTP, ISP, and TWAS toward work done in the author’s laboratory.

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Authors and Affiliations

  1. Department of Molecular Sciences, African Institute of Biomedical Science and Technology, Harare, Zimbabwe

    Collen Masimirembwa

  2. Department of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa

    Collen Masimirembwa

  3. Department of Pharmacology, Mayo Clinic, Rochester, MN, USA

    Alice Matimba

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  1. Collen Masimirembwa
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  2. Alice Matimba
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Correspondence to Collen Masimirembwa .

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  1. J. Craig Venter Institute (JCVI), 9704 Medical Center Drive, Rockville, 20850, Maryland, USA

    Karen E. Nelson

  2. KentHill Biosciences, 29 Carriage Walk Court, Gaithersburg, 20879, Maryland, USA

    Barbara Jones-Nelson

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Masimirembwa, C., Matimba, A. (2012). Pharmacogenomics in Africa. In: Nelson, K., Jones-Nelson, B. (eds) Genomics Applications for the Developing World. Advances in Microbial Ecology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-2182-5_11

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