Cyp2c19 Genotype and Omeprazole Hydroxylation Phenotype in Chinese Li Population

Abstract

1. CYP2C19 is a polymorphism of cytochrome P450, which is responsible for the metabolism of many drugs. The genetic polymorphism shows interethnic variation and it has been demonstrated that the frequency of poor metabolizers (PM) and the distribution of alleles of CYP2C19 vary among Chinese ethnic nationalities. The aim of the present study was to investigate the incidence of CYP2C19 polymorphism in the Chinese Li population. 2. One hundred and sixty-five unrelated healthy Li subjects were identified with respect to CYP2C19 by genotype and phenotype analysis. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping. The plasma concentrations of omeprazole and 5-hydroxyomeprazole were assayed by reversed-phase high-performance liquid chromatography and the omeprazole hydroxylation index (HI) was determined. 3. The frequency distribution of omeprazole HI is bimodal and the antimode for HI was estimated to be 5.6. The prevalence of phenotypic PM in the Li population was 16.6% (13.7-19.5; 95% CI). Genotype analysis revealed that the frequencies of the CYP2C19*1, *2 and *3 alleles in the Li population were 0.617 (0.590-0.644; 95% CI), 0.353 (0.327-0.379; 95% CI) and 0.031 (0.021-0.041; 95% CI), respectively. The frequency of genotypic PM was 14.7% (11.9-17.5; 95% CI), which almost agreed with the frequency of phenotypic PM. Omeprazole HI was significantly different among the different genotype groups (P < 0.05). 4. The present study revealed that the incidence of the CYP2C19*1, *2 and *3 alleles in Chinese Li population is different to that in other ethnic populations of China. There was an obvious relationship between CYP2C19 genotype and omeprazole hydroxylation phenotype, and about 90% of phenotypic PM can be explained by the CYP2C19*2 and *3 alleles.

Ligand-Based Design of a Potent and Selective Inhibitor of Cytochrome P450 2C19

“…11 Drugs that are metabolized in vivo by CYP2C19 include anticonvulsants such as phenytoin, psychotropic drugs such as imipramine and diazepam, and the proton pump inhibitors omeprazole, lansoprazole, and rabeprazole. 12 Proton pump inhibitors such as omeprazole block the release of gastric acid through inhibition of the H + /K + -ATPase pump in gastric parietal cells. 13 They are widely used to treat gastresophageal reflux disease (GERD) and Zollinger−Ellison syndrome.…”

“…CYP2C19 is a polymorphic enzyme that is localized in the liver (approximately 5% of hepatic P450) and intestine (less than 3% of intestinal P450). , The enzyme is inducible by rifampicin, phenobarbital, and dexamethasone. , The typical reactions used to monitor CYP2C19 activity include ( S ) - mephenytoin 4′-hydroxylation, omeprazole 5-hydroxylation, and fluoxetine O- demethylation with the choice of substrate playing an important role in the observed CYP2C19 activities and drug interaction profiles . Drugs that are metabolized in vivo by CYP2C19 include anticonvulsants such as phenytoin, psychotropic drugs such as imipramine and diazepam, and the proton pump inhibitors omeprazole, lansoprazole, and rabeprazole …”

Influence of CYP2C19 functional polymorphism on Helicobacter pylori eradication

“…CYP2C19*2 arises from G·A mutation at base pair (bp) 636 in exon 5 of wild-type (wt) CYP2C19*1 that creates an aberrant splice site. CYP2C19*3 involves a G·A mutation at bp 636 in exon 4 that creates a premature stop codon and a truncated protein (7,8).…”

Application of Population Pharmacokinetic Analysis to Characterize CYP2C19 Mediated Metabolic Mechanism of Voriconazole and Support Dose Optimization

“…The major variants of the CYP2C19 alleles in the Chinese population are *1, *2, *3, and *17 (Moriyama et al, 2017). The wild type (CYP2C19*1) is the most frequently found in our population, with a prevalence of about 60% (Fu et al, 2004;Wang et al, 2007;Zuo et al, 2012). The genotypic distributions of CYP2C19 in Chinese leads to phenotypes of poor metabolizers (PM), intermediate metabolizers (IM), normal metabolizers (NM),rapid metabolizers (RM)and ultrarapid metabolizers (UM).…”