Characterization of variants of CYP2D6 and CYP3A4 drug metabolizing enzymes among Ewe ethnic group in Ghana

Abstract

Studies have highlighted specific genetic traits linked to certain ethnic populations like the sickle cell anaemia being a genetic defect associated with African and African American populations. Allelic variants of drug metabolizing enzymes are no exception to this fundamental concept. Cytochrome P450 enzymes (CYPs) are responsible for metabolizing a major fraction of drugs with specific enzymes like CYP2D6 and 3A4 playing significant roles. Knowledge of individual/ethnic allelic variants of drug metabolizing enzymes as well as their resulting phenotypes can aid drug developers in providing individual/ethnic specific optimal dosages to improve therapeutic efficacy in Ghana. This study was aimed at determining the allelic type and frequency among the Ewe ethnic group in Ghana and their expected enzyme activity. The study entailed collection and genomic sequencing of whole blood samples from Ewe individuals in the Adidome (Southern part) and Hohoe (Northern) townships and genotypic analysis by Restrict digest of PCR amplified gene targets. From this study, the percentage of the Ewes in Ghana with the CYP2D6*3 and *4 variants were found to be 0.8% and 8.8% respectively which is consistent with studies done on other sub-Saharan populations. The frequency for the CYP3A4*1B, a variant responsible for decreased enzyme activity was found to be 2.42% of the sampled population of Ewes in Ghana, which varied from other previous studies done on varying Ghanaian populations with estimated ratios of 51%. Further studies on a larger sample size and different ethnic groups could pave the way for proper individualized drug therapy in Ghana.