title: The effect of the CYP2C19 genotype on the hydroxylation index of omeprazole in South Indians.
abstract: To investigate the relationship between CYP2C19 genotypes and the hydroxylation index (HI) of omeprazole in the South Indian population. Healthy unrelated South Indian subjects (n=300) were separated into three groups based on their CYP2C19 genotypes. They were administered a single oral dose of 20 mg omeprazole, and venous blood was collected 3 h later. Plasma was assayed using reversed-phase high-performance liquid chromatography, and the omeprazole HI was calculated. The means of HIs in individuals with CYP2C19*1/*1 (n=124), *1/*2 (n=129) and *2/*2,*2/*3 (n=47) were 2.4, 5.3 and 22.5, respectively, and were found to be significantly different between any two groups (P<0.0001). A good correlation was established between CYP2C19 genotype and omeprazole HI (r=0.54, 95% CI 0.45-0.62; P<0.0001). Of the 300 subjects, 42 (14.0%; 95% CI 10.1-17.9) were phenotypic poor metabolizers (PMs), but only 33 of them had two mutant alleles and the remaining 9 PMs had at least one wild-type allele. Among the 258 extensive metabolizers, 14 had two mutant alleles. The prevalence of PMs in the South Indian population was 14.0%, which is similar to that in North Indians and Orientals but significantly higher than in Caucasians and Africans. A genotype-phenotype relationship was established between the CYP2C19 genotype and HI of omeprazole, but 7.7% of subjects deviated from expected genotype-phenotype associations. This could be due to an additional mutation, either in the exons/introns or in the 5'-regulatory region of the CYP2C19 gene.
authors.affiliation: Department of Pharmacology, Pharmacogenomics Laboratory, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: J
authors.initials: J
authors.lastname: Rosemary
authors.forename: C
authors.initials: C
authors.lastname: Adithan
authors.forename: N
authors.initials: N
authors.lastname: Padmaja
authors.forename: C H
authors.initials: CH
authors.lastname: Shashindran
authors.forename: N
authors.initials: N
authors.lastname: Gerard
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D007194:India; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000378:metabolism*; D010597:Pharmacogenetics; D010641:Phenotype
chemical_list: D000897:Anti-Ulcer Agents; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole