Cytochrome P450 pharmacogenetics in African populations: implications for public health

Abstract

Introduction: Africa harbors a disproportionate burden of disease when taking into account the triple challenge caused by HIV/AIDS, tuberculosis (TB) and malaria, against a backdrop of an increasing burden of noncommunicable diseases. More than 80% of therapeutic drugs used in the management of these diseases/conditions are metabolized by CYP enzymes that exhibit genetic polymorphisms.

Areas covered: There is variability in the expression and activities of CYPs resulting in interindividual differences in the response to standard doses of therapeutic drugs, due to genetic polymorphisms, which exhibit both quantitative and qualitative differences between racial and between ethnic groups. The review aims to evaluate the implications of the genetic variation in CYPs on the public health of Africans. The CYPs reviewed here metabolize most of the commonly used therapeutic drugs and include CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 and 3A5. Allele frequencies are compared between African ethnic groups and among populations of African, Asian and European origin. Data are obtained from our own studies and literature.

Expert opinion: The variability in the pattern of genetic variation between populations translates into differences in drug response. Understanding CYP variability improves rational drug use and has public health significance.

Keywords::

• Africa
• cytochrome P450
• genetic diversity
• genetics variation
• pharmacogenetics
• pharmacogenomics
• public health

Declaration of interest

Funding for this work was from the Medical Research Council (MRC) of South Africa, National Research Foundation (NRF) and University of Cape Town for C Dandara. C Masimirembwa is an EDCTP Senior Clinical Research Fellow. M Swart and B Mpeta are postgraduate students in the Pharmacogenomics and Cancer Research group. C Dandara is the leader of the Pharmacogenetics Research Group in the Division of Human Genetics. A Wonkam is a Senior Medical Genetics Specialist.

Notes

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