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

To align predicted and measured CYP2C19 phenotype in a South African cohort. 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...

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Veröffentlicht in:Pharmacogenomics 2015-08, Vol.16 (12), p.1343-1354
Hauptverfasser: Dodgen, Tyren M, Drögemöller, Britt I, Wright, Galen E B, Warnich, Louise, Steffens, Francois E, Cromarty, A Duncan, Alessandrini, Marco, Pepper, Michael S
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Sprache:eng
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Zusammenfassung:To align predicted and measured CYP2C19 phenotype in a South African cohort. 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. 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. 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.
ISSN:1462-2416
1744-8042
DOI:10.2217/PGS.15.80