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Polymorphisms in CYP2C8 and CYP3A5 genes in the Nigerian population
Ayorinde Adehin1, Oluseye Oladotun Bolaji1, Martin A Kennedy2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
Abstract:
Polymorphisms in CYP2C8 and CYP3A5 genes have implications for responses elicited by the ingestion of some xenobiotics, the metabolism of which are mediated by these enzymes. CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A5*6 and CYP3A5*7 are a few functionally-relevant variants of these genes which this study provides data for, in the Nigerian population. Blood samples were processed for genomic DNA from 178 unrelated subjects spread across Nigerian ethnicities and screened for these polymorphism through the Sequenom iPLEX MassARRAY platform. Results obtained were further validated with Sanger sequencing of a few samples and thereafter, the genotype data were statistically processed. All alleles were in Hardy-Weinberg equilibrium and CYP2C8*2 occurred at a frequency (95% CI) of 0.194 (0.154, 0.239), while CYP3A5*3, CYP3A5*6 and CYP3A5*7 were found at frequencies (95% CI) of 0.160 (0.124, 0.202), 0.096 (0.067, 0.131) and 0.126 (0.094, 0.166), respectively. However, CYP2C8*3 was not detected in the population. The study observed a 60% prevalence of carriers of at least a CYP3A5 polymorphism in the population, suggesting the probable existence of huge variability in CYP3A5 activity which may prove significant in the administration of drugs with narrow therapeutic windows and whose metabolism is largely mediated by CYP3A5.
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