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

摘要

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 wasperformed 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 metabolite5’-hydroxyomperazole. RESULTS : Partial genotype-phenotype discrepancies were reported, and anadapted AS system was developed, which showed a marked improvement in phenotypeprediction. Results highlight the need for a more comprehensive CYP2C19 genotyping approachto improve prediction of omeprazole metabolism. CONCLUSION : Evidence for the utility of aCYP2C19 AS system is provided, for which the accuracy can be further improved by means ofcomprehensive genotyping and substrate specific modification.