Skip to main content
Log in

Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients

  • Short Communication
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Eradication of Helicobacter pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. The principal enzyme involved in PPIs metabolism is CYP2C19, which exhibits an interindividual variability of activity, mainly due to genetic polymorphism. Two alleles (CYP2C19*2 and CYP2C19*3), responsible for slow PPIs metabolism, were previously associated with higher efficacy of eradication. Recently, a novel CYP2C19 gene variant (CYP2C19*17), associated with faster metabolism of CYP2C19 substrates, was described. In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients.

Methods

A total of 125 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole+amoxicillin+metronidazole). Subsequently, the patients were divided into two groups (group 1 – success, and group 2 – failure of eradication after therapy) and genotyped for the presence of CYP2C19 variant alleles (*2, *3, and *17).

Results

Frequency of CYP2C19 alleles in two groups of patients were: 56.4 versus 65 (p=0.060) for *1, 15.4 versus 5.3 (p=0.015) for *2, and 28.2 versus 25.5 (p=0.663) for *17 allele, respectively. CYP2C19*3 was not detected in the evaluated population. No significant differences in frequency nor distribution of *17 allele were found between two groups of patients. CYP2C19*2 allele was associated with successful H. pylori eradication (p<0.02), *2 allele carriers were found to be over 4-times more prone to the treatment compared to *1/*1 homozygotes (OR=4.2, p=0.015).

Conclusion

Our results suggest that, contrary to CYP2C19*2, CYP2C19*17 allele has no impact on efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Andersson T, Regardh CG, Dahl-Puustinen ML, Bertilsson L (1990) Slow omeprazole metabolizers are also poor S-mephenytoin hydroxylators. Ther Drug Monit 12:415–416. 3

    PubMed  CAS  Google Scholar 

  2. Andersson T, Flockhart DA, Goldstein DB, Huang SM, Kroetz DL, Milos PM, Ratain MJ, Thummel K (2005) Drug-metabolizing enzymes: evidence for clinical utility of pharmacogenomic tests. Clin Pharmacol Ther 78:559–581

    Article  PubMed  CAS  Google Scholar 

  3. Boyanova L, Mentis A, Gubina M, Rozynek E, Gosciniak G, Kalenic S, Goral V, Kupcinskas L, Kantarceken B, Aydin A, Archimandritis A, Dzierzanowska D, Vcev A, Ivanova K, Marina M, Mitov I, Petrov P, Ozden A, Popova M (2002) The status of antimicrobial resistance of Helicobacter pylori in eastern Europe. Clin Microbiol Infect 8:388–396

    Article  PubMed  CAS  Google Scholar 

  4. Furuta T, Shirai N, Takashima M, Xiao F, Hanai H, Sugimura H, Ohashi K, Ishizaki T, Kaneko E (2001) Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Clin Pharmacol Ther 69:158–168

    Article  PubMed  CAS  Google Scholar 

  5. Furuta T, Shirai N, Watanabe F, Honda S, Takeuchi K, Iida T, Sato Y, Kajimura M, Futami H, Takayanagi S, Yamada M, Ohashi K, Ishizaki T, Hanai H (2002) Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther 72:453–460

    Article  PubMed  CAS  Google Scholar 

  6. Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T (2005) Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet 20:153–167

    Article  PubMed  CAS  Google Scholar 

  7. Gawronska-Szklarz B, Wrzesniewska J, Starzynska T, Pawlik A, Safranow K, Ferenc K, Drozdzik M (2005) Effect of CYP2C19 and MDR1 polymorphisms on cure rate in patients with acid-related disorders with Helicobacter pylori infection. Eur J Clin Pharmacol 61:375–379

    Article  PubMed  CAS  Google Scholar 

  8. Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM, Ghanayem BI (1994) Evidence that CYP2C19 is the major (S)-mephenytoin 4′-hydroxylase in humans. Biochemistry 33:1743–1752

    Article  PubMed  CAS  Google Scholar 

  9. Goldstein JA, Blaisdell J (1996) Genetic tests which identify the principal defects in CYP2C19 responsible for the polymorphism in mephenytoin metabolism. Methods Enzymol 272:210–218

    PubMed  CAS  Google Scholar 

  10. Grayson ML, Eliopoulos GM, Ferraro MJ, Moellering Jr RC (1989) Effect of varying pH on the susceptibility of Campylobacter Eliopoulos GM pylori to antimicrobial agents. Eur J Clin Microbiol Infect Dis 8:888–889

    Article  PubMed  CAS  Google Scholar 

  11. Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P (1991) A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques 11:298–300, 302

    CAS  Google Scholar 

  12. Kupfer A, Preisig R (1984) Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol 26:753–759

    Article  PubMed  CAS  Google Scholar 

  13. Scott D, Weeks D, Melchers K, Sachs G (1998) The life and death of Helicobacter pylori. Gut 43 Suppl 1:S56–S60

    Article  PubMed  CAS  Google Scholar 

  14. Shimatani T, Inoue M, Kuroiwa T, Horikawa Y, Mieno H, Nakamura M (2003) Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2-receptor antagonist. Aliment Pharmacol Ther 18:1149–1157

    Article  PubMed  CAS  Google Scholar 

  15. Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, Ingelman-Sundberg M (2006) A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79:103–113

    Article  PubMed  CAS  Google Scholar 

  16. Yamazaki H, Inoue K, Shaw PM, Checovich WJ, Guengerich FP, Shimada T (1997) Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples. J Pharmacol Exp Ther 283:434–442

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marek Droździk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kurzawski, M., Gawrońska-Szklarz, B., Wrześniewska, J. et al. Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients. Eur J Clin Pharmacol 62, 877–880 (2006). https://doi.org/10.1007/s00228-006-0183-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-006-0183-2

Keywords

Navigation