Evaluation of predictive CYP2C19 genotyping assays relative to measured phenotype in a South African cohort

Author:

Dodgen Tyren M123,Drögemöller Britt I4,Wright Galen EB4,Warnich Louise4,Steffens Francois E5,Cromarty A Duncan1,Alessandrini Marco23,Pepper Michael S236

Affiliation:

1. Department of Pharmacology, University of Pretoria, Pretoria, South Africa

2. Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa

3. Institute for Cellular & Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

4. Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa

5. Department of Statistics, Faculty of Natural & Agricultural Sciences, University of Pretoria, Pretoria, South Africa

6. Department of Genetic Medicine & Development, Faculty of Medicine, University of Geneva, Switzerland

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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