Determination of CYP2C19 phenotype in black Americans with omeprazole: correlation with genotype.
BACKGROUND
Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype.


METHODS
This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic. Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications. Baseline omeprazole and 2-hour postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for phenotype determination. Identification of CYP2C19m1 genotypes were performed with use of the polymerase chain reaction.


RESULTS
Results were obtained for 28 men and 72 women. Ninety-eight subjects were found to be phenotypically extensive metabolizers and two to be poor metabolizers (one man; one smoker). Genotype determination revealed that the two poor metabolizers of omeprazole were homozygous for a single base pair mutation (m1/m1) in exon 5 of CYP2C19. Twenty-eight of the extensive metabolizers were heterozygous (m1/wt) and the remaining 70 were homozygous (wt/wt). No side effects were reported.


CONCLUSIONS
The 2% prevalence rate of poor CYP2C19 metabolizers in this healthy black population residing in the Midwestern United States is similar to that reported in white subjects and in the Shona population of Zimbabwe but much less than in Asian subjects. Omeprazole is a safe and specific probe of the CYP2C19 enzyme system that correlates well with genotype.
Marinac
J S
JS
Department of Medicine, University of Missouri-Kansas City, School of Medicine 64108, USA.
Balian
J D
JD
Foxworth
J W
JW
Willsie
S K
SK
Daus
J C
JC
Owen
R
R
Flockhart
D A
DA
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D044383:Black People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000097:blood*; D010641:Phenotype; D012016:Reference Values; D001741:Black or African American
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; C049963:5-hydroxymethylomeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole