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

Abstract

AIM : To align predicted and measured CYP2C19 phenotype in a South African cohort. MATERIALS AND 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.