CYP2C19 Activity Comparison Between Swedes and Koreans: Effect of Genotype, Sex, Oral Contraceptive Use, and Smoking

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 2010 May 26

PMID 20499227

Citations 22

Authors

Margareta Ramsjo

Eleni Aklillu

Lilleba Bohman

Magnus Ingelman-Sundberg

Hyung-Keun Roh

Leif Bertilsson

Affiliations

Soon will be listed here.

Abstract

Objectives: To compare CYP2C19 enzyme activity between Swedes and Koreans controlling for the effect of CYP2C19 genotype, sex, oral contraceptive use, and smoking habits.

Methods: CYP2C19 activity was determined in 185 healthy Swedish and 150 Korean subjects as the omeprazole/5-hydroxyomeprazole ratio (metabolic ratio; MR) using high-performance liquid chromatography. Genotyping was performed by PCR using Taqman assay.

Results: As expected, a higher incidence of poor metabolizers (PM) was found in Koreans (14%) compared with Swedes (3.8%) and the frequency of the CYP2C19 17 allele was very low in Koreans (0.3%). Among subjects homozygous for CYP2C19 1, Koreans displayed significantly lower CYP2C19 enzyme activity than Swedes (p < 0.000001). Interestingly, in Koreans a pronounced gender difference was apparent: females (n = 24) had significantly lower MR than males (n = 30; p < 0.0001), but such a gender difference was not seen among Swedes. Swedish OC users had a higher MR than non-users (p < 0.00001), whereas OC was only used by one Korean. No effects of smoking were observed.

Conclusions: We find specific gender-dependent effects of CYP2C19 activity in Koreans, but not in Swedes. Controlling for the effect of genotype and sex, Koreans display lower CYP2C19 activity than Swedes. The genetic, epigenetic or environmental basis for this difference remains to be identified.

Citing Articles

Impact of fresh grape juice on the pharmacokinetics of omeprazole: results of a food-drug interaction study.

Iftikhar T, Iqbal Z, Shah Y, Khan N, Abbas M, Shehzad O Front Pharmacol. 2024; 15:1467805.

PMID: 39697543 PMC: 11652163. DOI: 10.3389/fphar.2024.1467805.

A web-based scoping review assessing the influence of smoking and smoking cessation on antidiabetic drug meabolism: implications for medication efficacy.

Bellanca C, Augello E, Di Benedetto G, Burgaletto C, Cantone A, Cantarella G Front Pharmacol. 2024; 15:1406860.

PMID: 38957391 PMC: 11217182. DOI: 10.3389/fphar.2024.1406860.

Prediction of Omeprazole Pharmacokinetics and its Inhibition on Gastric Acid Secretion in Humans Using Physiologically Based Pharmacokinetic-Pharmacodynamic Model Characterizing CYP2C19 Polymorphisms.

Li S, Xie L, Yang L, Jiang L, Yang Y, Zhi H Pharm Res. 2023; 40(7):1735-1750.

PMID: 37226024 DOI: 10.1007/s11095-023-03531-y.

Pharmacokinetics and bioequivalence evaluation of omeprazole and sodium bicarbonate dry suspensions in healthy Chinese volunteers.

Zhang R, Guo P, Zhou J, Li P, Wan J, Yang C Sci Rep. 2023; 13(1):1113.

PMID: 36670124 PMC: 9859815. DOI: 10.1038/s41598-022-27286-5.

Efficacy and safety of combination antifungal therapy in Korean haematological patients with invasive aspergillosis.

Lee D, Lee H, Yan J, Lin S, Aram J Mycoses. 2019; 62(10):969-978.

PMID: 31355956 PMC: 7003761. DOI: 10.1111/myc.12972.

References

de Morais S, Wilkinson G, Blaisdell J, Nakamura K, Meyer U, Goldstein J . The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994; 269(22):15419-22. View

Suzuki T, Matsuo K, Sawaki A, Wakai K, Hirose K, Ito H . Influence of smoking and CYP2C19 genotypes on H. pylori eradication success. Epidemiol Infect. 2006; 135(1):171-6. PMC: 2870552. DOI: 10.1017/S0950268806006613. View

Chang M, Dahl M, Tybring G, Gotharson E, Bertilsson L . Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype. Pharmacogenetics. 1995; 5(6):358-63. DOI: 10.1097/00008571-199512000-00004. View

Christensen M, Andersson K, Dalen P, Mirghani R, Muirhead G, Nordmark A . The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther. 2003; 73(6):517-28. DOI: 10.1016/S0009-9236(03)00050-X. View

Alvan G, Bechtel P, Iselius L, Gundert-Remy U . Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol. 1990; 39(6):533-7. DOI: 10.1007/BF00316090. View

Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou H, Zhou B . Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese. Clin Pharmacol Ther. 1989; 46(2):198-207. DOI: 10.1038/clpt.1989.126. View

de Morais S, Wilkinson G, Blaisdell J, Meyer U, Nakamura K, Goldstein J . Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol. 1994; 46(4):594-8. View

Laine K, Tybring G, Bertilsson L . No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects. Clin Pharmacol Ther. 2000; 68(2):151-9. DOI: 10.1067/mcp.2000.108949. View

Andersson T, Miners J, Veronese M, Tassaneeyakul W, Meyer U, Birkett D . Identification of human liver cytochrome P450 isoforms mediating omeprazole metabolism. Br J Clin Pharmacol. 1993; 36(6):521-30. PMC: 1364656. DOI: 10.1111/j.1365-2125.1993.tb00410.x. View

10.

Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E . Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur J Clin Pharmacol. 2007; 64(4):381-5. DOI: 10.1007/s00228-007-0438-6. View

11.

Tamminga W, Wemer J, Oosterhuis B, Weiling J, Wilffert B, de Leij L . CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol. 1999; 55(3):177-84. DOI: 10.1007/s002280050615. View

12.

Tybring G, Bottiger Y, Widen J, Bertilsson L . Enantioselective hydroxylation of omeprazole catalyzed by CYP2C19 in Swedish white subjects. Clin Pharmacol Ther. 1997; 62(2):129-37. DOI: 10.1016/S0009-9236(97)90060-6. View

13.

Roh H, Dahl M, Tybring G, Yamada H, CHA Y, Bertilsson L . CYP2C19 genotype and phenotype determined by omeprazole in a Korean population. Pharmacogenetics. 1996; 6(6):547-51. DOI: 10.1097/00008571-199612000-00008. View

14.

Palovaara S, Tybring G, Laine K . The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects. Br J Clin Pharmacol. 2003; 56(2):232-7. PMC: 1884281. DOI: 10.1046/j.1365-2125.2003.01868.x. View

15.

Li X, Andersson T, Ahlstrom M, Weidolf L . Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004; 32(8):821-7. DOI: 10.1124/dmd.32.8.821. View

16.

Nakamura K, Goto F, Ray W, McALLISTER C, Jacqz E, Wilkinson G . Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther. 1985; 38(4):402-8. DOI: 10.1038/clpt.1985.194. View

17.

Sim S, Risinger C, Dahl M, Aklillu E, Christensen M, Bertilsson L . A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006; 79(1):103-13. DOI: 10.1016/j.clpt.2005.10.002. View

18.

Gomez A, Ingelman-Sundberg M . Pharmacoepigenetics: its role in interindividual differences in drug response. Clin Pharmacol Ther. 2009; 85(4):426-30. DOI: 10.1038/clpt.2009.2. View

19.

Brosen K . Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie. 2004; 59(1):5-12. DOI: 10.2515/therapie:2004003. View

20.

Xie H, Huang S, Xu Z, Xiao Z, He N, Zhou H . Evidence for the effect of gender on activity of (S)-mephenytoin 4'-hydroxylase (CYP2C19) in a Chinese population. Pharmacogenetics. 1997; 7(2):115-9. DOI: 10.1097/00008571-199704000-00004. View