African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development

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.

Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness

“…Hence, alternative drugs may be considered for managing pain in SCD patients with African ancestry. Although we did not find extensive CYP allele frequency variations among the African populations as reported in a previous study [76], our results also emphasize the need for the population targeted optimization and development of drugs.…”

“…There can be marked differences in the allele frequencies of important pharmacogenes among the sub-populations belonging to the same super-population. Such differences were observed in the allele frequencies of CYP genes in African populations [76]. There may be large allele frequency differences even among groups of the same population.…”

Cytochrome P450 CYP2B6*6 distribution among Congolese individuals with HIV, Tuberculosis and Malaria infection

“…Alternatively, heterogeneity among different ethnic populations in this geographical region cannot be excluded (Gounden et al, 2010;Klein et al, 2005;Kwara et al, 2009;Mehlotra et al, 2006;Nyakutira et al, 2008). Corroborating our findings, studies from Uganda and Zimbabwe document a high frequency of the studied CYP2B6*6 variant (66-68%) (Rajman et al, 2017).…”

Clinical Utilization of Pharmacogenetics in Psychiatry – Perspectives of Pharmacists, Genetic Counselors, Implementation Science, Clinicians, and Industry

“…In fact, 54 % of clinicians cited the lack of clinical practice guidelines on how to utilize PGx testing and 43 % cited cost as top barriers to utilizing PGx testing in practice [116]. When it comes to the actual science behind PGx testing, most of the data are from clinical trials in Caucasians; therefore, the prevalence of variants and effect of current PGx interpretation on outcomes for other ethnicities is not well established [119,120]. Many PGx studies also focus on the effect of single genes, resulting in insufficient evidence for clinical utility and frustration from the field.…”