African variation at Cytochrome P450 genes
Open Access
- 15 May 2013
- journal article
- Published by Oxford University Press (OUP) in Evolution, Medicine, and Public Health
- Vol. 2013 (1), 118-134
- https://doi.org/10.1093/emph/eot010
Abstract
The genomics revolution has provided a plethora of data from many previously uncharacterized populations. The increase in the amount of genetic data has improved our understanding of why individuals and populations differ in their susceptibility to multiple diseases. It has also enabled researchers to identify how genomic variation, including at the Cytochrome P450 (CYP450) super-family, affects the safety and efficacy of therapeutic drugs. CYP450 metabolize ∼90% of clinically administered drugs. Variability in CYP450 expression is known to affect the safety and efficacy of therapeutic drugs, including many used in the treatment and control of infectious diseases. There are inter-ethnic differences in the frequencies of clinically relevant CYP450 variants which affect CYP450 expression. Comparative studies of African populations have identified population structuring at CYP450 genes. This is associated with intra-African differences in the success of drug therapies used in the treatment of infectious diseases. Therapeutic drugs dominate control strategies for infectious diseases and are widely administered through mass drug administration campaigns. However, resistance to chemotherapy is spreading across endemic regions. The most common response has been to increase chemotherapeutic dosages, and administer combination therapies. However, there are few pharmacovigilance data examining how these changes influence adverse drug reactions. This review provides an overview of current knowledge of intra-Africa CYP450 variation, and the known associations with sub-optimal clinical outcomes in the treatment of infectious diseases. In addition, the potential for evolutionary approaches in the study of CYP450 variation is discussed to examine their potential in preventative medicine and intervention strategies within Africa.This publication has 93 references indexed in Scilit:
- Molecular diversity and population structure at the Cytochrome P450 3A5 gene in AfricaBMC Genetics, 2013
- Influence of CYP3A4, CYP3A5 and MDR-1 polymorphisms on tacrolimus pharmacokinetics and early renal dysfunction in liver transplant recipientsGene, 2013
- Identification of Cytochrome P450 Oxidoreductase Gene Variants That Are Significantly Associated with the Interindividual Variations in Warfarin Maintenance DoseDrug Metabolism and Disposition, 2011
- Global patterns of genetic diversity and signals of natural selection for human ADME genesHuman Molecular Genetics, 2010
- CYP1A2 is more variable than previously thought: a genomic biography of the gene behind the human drug-metabolizing enzymePharmacogenetics and Genomics, 2010
- Artemisinin Resistance inPlasmodium falciparumMalariaThe New England Journal of Medicine, 2009
- The Genetic Structure and History of Africans and African AmericansScience, 2009
- Global variation in CYP2C8–CYP2C9 functional haplotypesThe Pharmacogenomics Journal, 2009
- Ethnic differences in the distribution ofCYP3A5gene polymorphismsXenobiotica, 2006
- The global distribution of clinical episodes of Plasmodium falciparum malariaNature, 2005