Department of Pharmacology, University of Pretoria, Pretoria, South Africa; Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria, South Africa; Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa; Department of Statistics, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Switzerland
Dodgen, T.M., Department of Pharmacology, University of Pretoria, Pretoria, South Africa, Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria, South Africa, Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Drögemöller, B.I., Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa; Wright, G.E.B., Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa; Warnich, L., Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa; Steffens, F.E., Department of Statistics, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa; Cromarty, A.D., Department of Pharmacology, University of Pretoria, Pretoria, South Africa; Alessandrini, M., Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria, South Africa, Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Pepper, M.S., Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria, South Africa, Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa, Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Switzerland
Aim: To align predicted and measured CYP2C19 phenotype in a South African cohort. Materials & methods: Genotyping of CYP2C19∗2, ∗3, ∗9, ∗15, ∗17, ∗27 and ∗28 was performed using PCR-RFLP, and an activity score (AS) system was used to predict phenotype. True phenotype was measured using plasma concentrations of omeprazole and its metabolite 5′-hydroxyomperazole. Results: Partial genotype-phenotype discrepancies were reported, and an adapted AS system was developed, which showed a marked improvement in phenotype prediction. Results highlight the need for a more comprehensive CYP2C19 genotyping approach to improve prediction of omeprazole metabolism. Conclusion: Evidence for the utility of a CYP2C19 AS system is provided, for which the accuracy can be further improved by means of comprehensive genotyping and substrate-specific modification. © 2015 Future Medicine Ltd.