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African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development
- Source :
- EBioMedicine, Vol 17, Iss C, Pp 67-74 (2017), EBioMedicine
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Genetic diversity is greater in Africa than in other continental populations. Genetic variability in genes encoding drug metabolizing enzymes may contribute to the high numbers of adverse drug reactions reported in Africa. We reviewed publications (1995–April 2016) reporting frequencies of known cytochrome P450 (CYP) variants in African populations. Using principal components analysis (PCA) we identified CYP alleles of potential clinical relevance with a marked difference in distribution in Africa, compared with Asian and Caucasian populations. These were CYP2B6*6, CYP2C8*2, CYP2D6*3, CYP2D6*17, CYP2D6*29, CYP3A5*6, and CYP3A5*7. We show clearly that there is greater diversity in CYP distribution in Africa than in other continental populations and identify a need for optimization of drug therapy and drug development there. Further pharmacogenetic studies are required to confirm the CYP distributions we identified using PCA, to discover uniquely African alleles and to identify populations at a potentially increased risk of drug-induced adverse events or drug inefficacy.<br />Highlights • Greater diversity in CYP450 distribution in Africa vs Europe or Asia was demonstrated. • CYP alleles with a marked difference in distribution in Africa were identified. • CYP alleles that may be uniquely African were highlighted. • These data may help to identify regions at a greater risk of adverse drug reactions. Genetic diversity is greater in Africa than in other populations, yet in clinical therapeutics and drug development Africa is often treated as a homogenous, single entity. Genetic diversity in cytochrome P450 (CYP) genes may contribute to high numbers of adverse drug reactions reported in Africa. Reports on polymorphisms in drug metabolizing enzymes in African populations are limited. Our study demonstrates greater genetic diversity in CYPs in Africa and identifies CYP alleles with markedly different distribution in Africa compared with other populations. Our data can help identify African regions at potentially greater risk of adverse drug reactions or drug inefficacy.
- Subjects :
- 0301 basic medicine
CYP2B6
Black People
lcsh:Medicine
CYP450
Drug development
Biology
030226 pharmacology & pharmacy
digestive system
General Biochemistry, Genetics and Molecular Biology
Genetic diversity
03 medical and health sciences
0302 clinical medicine
Cytochrome P-450 Enzyme System
Gene Frequency
Drug Discovery
Humans
Genetic variability
Allele
Adverse effect
CYP3A5
Genetics
Drug metabolism
lcsh:R5-920
Polymorphism, Genetic
lcsh:R
General Medicine
3. Good health
030104 developmental biology
Pharmacogenetics
Africa
lcsh:Medicine (General)
Research Paper
Subjects
Details
- ISSN :
- 23523964
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....638a8f56e845769e41a2fdbe4f51ab12
- Full Text :
- https://doi.org/10.1016/j.ebiom.2017.02.017