title: Evaluation of predictive CYP2C19 genotyping assays relative to measured phenotype in a South African cohort.
abstract: OBJECTIVE
  To align predicted and measured CYP2C19 phenotype in a South African cohort.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, University of Pretoria, Pretoria, South Africa.|Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.|Institute for Cellular & Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Tyren M
authors.initials: TM
authors.lastname: Dodgen
authors.affiliation: Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Britt I
authors.initials: BI
authors.lastname: Drögemöller
authors.affiliation: Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Galen E B
authors.initials: GE
authors.lastname: Wright
authors.affiliation: Department of Genetics, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Louise
authors.initials: L
authors.lastname: Warnich
authors.affiliation: Department of Statistics, Faculty of Natural & Agricultural Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Francois E
authors.initials: FE
authors.lastname: Steffens
authors.affiliation: Department of Pharmacology, University of Pretoria, Pretoria, South Africa.
authors.forename: A Duncan
authors.initials: AD
authors.lastname: Cromarty
authors.affiliation: Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.|Institute for Cellular & Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Marco
authors.initials: M
authors.lastname: Alessandrini
authors.affiliation: Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.|Institute for Cellular & Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.|Department of Genetic Medicine & Development, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000378:metabolism; D010641:Phenotype; D013019:South Africa
chemical_list: C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole
keywords: CYP2C19; South Africa; activity score system; genotype–phenotype correlation; omeprazole