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

• Published in: Pharmacogenomics Vol. 16; no. 12; pp. 1343 - 1354
• Main Authors: Dodgen, Tyren M, Drögemöller, Britt I, Wright, Galen E B, Warnich, Louise, Steffens, Francois E, Cromarty, A Duncan, Alessandrini, Marco, Pepper, Michael S
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.08.2015
• Subjects: Adult; African Continental Ancestry Group - genetics; Cytochrome P-450; Cytochrome P-450 CYP2C19 - genetics; Drug metabolism; Female; Genetic aspects; Genotype; Humans; Identification and classification; Inactivation, Metabolic - genetics; Male; Middle Aged; Omeprazole - metabolism; Phenotype; Phenotypes; Properties; South Africa; South Africans; genotype–phenotype correlation; South Africa; omeprazole; CYP2C19; activity score system
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/PGS.15.80

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.