CYP3A and CYP2C19 activity in urine in relation to CYP3A4, CYP3A5, and CYP2C19 polymorphisms in Russian peptic ulcer patients taking omeprazole

• Published in: Pharmacogenomics and personalized medicine Vol. 11; pp. 107 - 112
• Main Authors: Denisenko, Natalia P, Sychev, Dmitriy A, Sizova, Zhanna M, Smirnov, Valeriy V, Ryzhikova, Kristina A, Sozaeva, Zhannet A, Grishina, Elena A
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Cytochrome; Cytochrome P-450; Deoxyribonucleic acid; DNA; Duodenal ulcer; EDTA; Enzymes; Equilibrium; Gene expression; Genetic aspects; Genotype & phenotype; Genotypes; Glucocorticoids; Hormones; Liquid chromatography; Metabolism; Metabolites; metabolomics; Omeprazole; Original Research; Peptic ulcer; pharmacogenetics; Pharmacogenomics; phenotyping; Polymerase chain reaction; Polymorphism; Professional education; proton pump inhibitor; Proton pump inhibitors; Spectroscopy; Statistical analysis; Steroids (Organic compounds); Ulcers; Urine; United States > US; Russia; metabolomics; phenotyping; proton pump inhibitor; pharmacogenetics
• ISSN: 1178-7066; 1178-7066
• DOI: 10.2147/PGPM.S159708

Proton pump inhibitors (PPIs) are metabolized by cytochrome P450. CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a secondary enzyme for PPI biotransformation.
The aim of the study was to find if
, and
genotypes are connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients taking omeprazole.
Forty-eight gastric or duodenal ulcer patients (15 men, 33 women; mean age 55.0±15.3 years, age range 18-91 years) from Moscow region of Russia were enrolled. Peripheral venous blood was collected for DNA extraction, and real-time polymerase chain reaction was performed for
(rs776746),
C>T in intron
(rs35599367),
(rs4244285),
(rs4986893), and
(rs12248560) polymorphism analyses. Urine samples of patients were collected in the morning between 6 and 9 am before food or drug intake. Urine cortisol and 6β-hydroxycortisol concentrations (for CYP3A activity) and omeprazole and 5-hydroxyomeprazole concentrations (for CYP2C19 activity) were measured using high-performance liquid chromatography/mass spectroscopy.
We found a connection between
genotypes and CYP3A activity. Median metabolic ratios 6β-hydroxycortisol/cortisol (25%-75% percentiles) were 2.84 (1.99-4.39) for CYP2C19 extensive metabolizers (EMs), 2.51 (1.86-4.73) for CYP2C19 ultra-rapid metabolizers (UMs), and 1.45 (1.12-2.16) for CYP2C19 intermediate metabolizers (IMs) + poor metabolizers (PMs). A statistically significant difference in CYP3A activity (Mann-Whitney test) was found between CYP2C19 EMs vs CYP2C19 IMs+PMs (
=0.006), between CYP2C19 UMs vs CYP2C19 IMs+PMs (
=0.018), and in multiple comparison Kruskal-Wallis test (
=0.014).
In CYP2C19 IMs+PMs, CYP3A activity was significantly lower than in CYP2C19 EMs and UMs.