The effect of the genetic polymorphism of CYP2C19 on the effectiveness of eradication of Helicobacter pylori infection, a key factor in gastric carcinogenesis

Background. Helicobacter pylori infection is a major risk factor for gastric cancer, and its eradication is considered a primary preventive measure. Proton pump inhibitors (PPIs) are a cornerstone of eradication therapy, but their efficacy is significantly influenced by genetic polymorphisms in the CYP2C19 enzyme, which is responsible for their metabolism.

Objective. To summarize and present current research on the impact of CYP2C19 genetic polymorphism on the effectiveness of H. pylori eradication therapy.

Materials and methods. A literature review was conducted using Russian and international databases (RSCI, PubMed, ResearchGate) with keywords including "CYP2C19 polymorphism," "proton pump inhibitor metabolism," and "Helicobacter pylori eradication." A total of 41 publications most relevant to the topic were analyzed.

Results. The metabolism of first-generation PPIs (omeprazole, lansoprazole, pantoprazole) is highly dependent on CYP2C19 activity. Patients are classified into different metabolic phenotypes (ultrarapid – UM, rapid – RM, normal – NM, intermediate – IM, poor – PM) based on their CYP2C19 genotype. Evidence, primarily from Asian populations, indicates that NM and RM/UM phenotypes are associated with lower eradication rates due to accelerated PPI metabolism and reduced drug exposure, whereas IM and PM phenotypes show higher efficacy. The Russian population has a high frequency of the rapid metabolizer allele CYP2C19*17, suggesting potential suboptimal response to standard PPI doses. Rabeprazole and esomeprazole demonstrate less dependence on CYP2C19, leading to more consistent efficacy across different genotypes. Clinical guidelines (e.g., CPIC, DPWG) recommend genotype-guided PPI dosing to optimize therapy.

Conclusion. CYP2C19 genetic polymorphism is a critical determinant of PPI pharmacokinetics and the effectiveness of H. pylori eradication. Pharmacogenetic testing for CYP2C19 can be a valuable tool for personalizing anti-Helicobacter therapy, particularly in populations with a high prevalence of rapid metabolizer alleles, by enabling the selection of the most appropriate PPI and its dose to overcome refractoriness and improve treatment outcomes.

1. Andreev DN, Khurmatullina AR, Bordin DS, Maev IV. Trends in the prevalence of Helicobacter pylori infection among adults in Moscow: a systematic review and meta-analysis. Terapevticheskii Arkhiv (Ter. Arkh.). 2025;97(5):463-470. (In Russ.). doi: 10.26442/00403660.2025.05.203250.

2. Bordin DS, Kuznetsova ES, Stauver EE, et al. Epidemiology of Helicobacter pylori infection in the Russian Federation from 1990 to 2023: a systematic review. Russian Medical Inquiry. 2024;8(5):260-267. (In Russ.). doi: 10.32364/25876821-2024-8-5-3.

3. Ruta AV, Luchinina EV, Shelekhova TV, et al. Relationship between CYP2C19 genotypes and proton pump inhibitorsʹs pharmacokinetics and pharmacodynamics: review. South Russian Journal of Therapeutic Practice. 2024;5(1):15-22. (In Russ.). doi: 10.21886/2712-8156-2024-5-1-15-22.

4. Malignant Neoplasms in Russia in 2023 (Incidence and Mortality) / edited by A.D. Kaprin [et al.] Moscow: P.A. Herzen Moscow Research Institute of Oncology – branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 2024. 276 p. (In Russ.). ISBN 978-5-85502-298-8.

5. Tikhonov SV, Kareva EN, Serebrova SYu, et al. New achievements of pharmacology for practical medicine in prevention and therapy of acid-dependent diseases. Meditsinskiy Sovet. 2023;17(8):33-40. (In Russ.)]. doi: 10.21518/ms2023-133.

6. Perfilova KM, Butina TYu, Neumoina NV, et al. Polymorphism of the CYP2C19 gene in newly diagnosed and persistent Helicobacter pylori infection. In: Infectious diseases in the modern world: evolution, current and future threats. Moscow, 2023. Pp. 173-174. (In Russ.).

7. Ivashkin VT, Lapina TL, Maev IV, et al Clinical Practice Guidelines of Russian Gastroenterological Association, Scientific Society for the Clinical Study of Human Microbiome, Russian Society for the Prevention of Non-Communicable Diseases, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy for Н. pylori Diagnostics and Treatment in Adults. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(6):72-93. (In Russ.). doi: 10.22416/1382-4376-202232-6-72-93.

8. Sychev DA, Abdullaev ShP, Ametov AS. [et al.]]; ed by DA Sychev. Moscow: Triad Publ., 2021. (In Russ.). ISBN 978-5-94789-982-5.

9. Kareva EN. Pharmacogenetic management concerning efficacy and safety of proton-pump inhibitors. RMJ. 2021;29(4):68-73. (In Russ.).

10. Neumoina MI, Shmakova TV, Perfilova KM, et al. Effects of CYP2C19 Polymorphism on Metabolism and Effectiveness of Proton Pump Inhibitors: A Review of Clinical and Laboratory Studies. Public Health and Life Environment – PH&LE. 2021;(4):66-73. (In Russ.). doi: 10.35627/2219-5238/2021-337-4-66-73.

11. Ivashkin VT, Maev IV, Tsar’kov PV, et al. Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, Russian Society of Colorectal Surgeons and the Russian Endoscopic Society). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(1):49-70. (In Russ.). doi: 10.22416/1382-4376-202030-1-49-70.

12. Denisenko NP, Sychev DA, Sizova ZM, et al. CYP3A and CYP2C19 activity in urine in relation to CYP3A4, CYP3A5, and CYP2C19 polymorphisms in Russian peptic ulcer patients taking omeprazole. Pharmgenomics Pers Med. 2018 Jun 18;11:107-112. doi: 10.2147/PGPM.S159708.

13. Denisenko NP, Sychev DA, Sizova ZhM, et al. Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in slavic patients with peptic ulcers: a meta-analysis. Eksperimental’naya i Klinicheskaya Gastroenterologiya. 2016;135(11):11-16. (In Russ.).

14. Malfertheiner P, Megraud F, Rokkas T, et al.; European Helicobacter and Microbiota Study group. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Aug 8:gutjnl-2022-327745. doi: 10.1136/gutjnl-2022-327745.

15. Rugge M, Genta RM, Malfertheiner P, et al; RE.GA.IN; RE GA IN. RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates. Gut. 2024 Feb 23;73(3):407-441. doi: 10.1136/gutjnl-2023-331164.

16. Shirani M, Pakzad R, Haddadi MH, et al. The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis. BMC Infect Dis. 2023 Aug 19;23(1):543. doi: 10.1186/s12879023-08504-5.

17. Lemos FFB, de Castro CT, Calmon MS, et al. Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis. World J Gastroenterol. 2023 Apr 14;29(14):2202-2221. doi: 10.3748/wjg.v29.i14.2202.

18. Ford AC, Yuan Y, Moayyedi P. Long-Term Impact of Helicobacter pylori Eradication Therapy on Gastric Cancer Incidence and Mortality in Healthy Infected Individuals: A Meta-Analysis Beyond 10 Years of Follow-Up. Gastroenterology. 2022 Sep;163(3):754-756.e1. doi: 10.1053/j.gastro.2022.05.027.

19. Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Abate D, Abbasi N, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2019 Dec 1;5(12):1749-1768. doi: 10.1001/jamaoncol.2019.2996.

20. De Francesco V, Manta R, Marmo R, et al. Efficacy of Helicobater pylori eradication in patients with diffuse large B-cell lymphoma of the stomach: A systematic review. Eur J Haematol. 2022 Dec;109(6):643-647. doi: 10.1111/ejh.13871.

21. Mülder DT, Hahn AI, Huang RJ, et al. Prevalence of Gastric Precursor Lesions in Countries With Differential Gastric Cancer Burden: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2024 Aug;22(8):1605-1617. e46. doi: 10.1016/j.cgh.2024.02.023.

22. Wu Z, Tang Y, Tang M, et al. The relationship between the eradication of Helicobacter pylori and the occurrence of stomach cancer: an updated metaanalysis and systemic review. BMC Gastroenterol. 2025 Apr 21;25(1):278. doi: 10.1186/s12876-025-03886-z.

23. Zhu F, Zhang X, Li P, Zhu Y. Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis. Helicobacter. 2023 Dec;28(6):e13013. doi: 10.1111/hel.13013.

24. Malfertheiner P, Bornschein J, Selgrad M. Role of Helicobacter pylori infection in gastric cancer pathogenesis: a chance for prevention. J Dig Dis. 2010 Feb;11(1):2-11. doi: 10.1111/j.1751-2980.2009.00408.x.

25. Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention. Nat Rev Clin Oncol. 2023 May;20(5):338-349. doi: 10.1038/s41571-023-00747-0. Epub 2023 Mar 23. PMID: 36959359.

26. Thuy LLT, Nguyen LT, Vu HA, et al. Effect of MDR1 C3435T and CYP2C19 genetic polymorphisms on the outcome of Helicobacter pylori eradication treatment in children with gastritis and peptic ulcer, Vietnam. BMC Pediatr. 2024 Jul 19;24(1):464. doi: 10.1186/s12887-024-04581-w.

27. Liu Y, Zhu X, Li R, et al. Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: insights from a single-centred retrospective study. BMJ Open. 2020 Nov 26;10(11):e040473. doi: 10.1136/bmjopen2020-040473.

28. Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423. doi: 10.1002/ cpt.2015.

29. Chenchula S, Atal S, Jhaj R, Uppugunduri CRS. Implementing pharmacogenetic testing to optimize proton-pump inhibitors use among Indian population based on CPIC-CYP2C19-PPI dosing guidelines: The need of the hour. Indian J Pharmacol. 2024 Jul 1;56(4):277-284. doi: 10.4103/ijp.ijp_198_24.

30. El Rouby N, Lima JJ, Johnson JA. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):447-460. doi: 10.1080/17425255.2018.1461835.

31. Weitzel KW, Elsey AR, Langaee TY, et al. Clinical pharmacogenetics implementation: approaches, successes, and challenges. Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):56-67. doi: 10.1002/ajmg.c.31390.

32. Pharmacogenomics Knowledgebase (PharmGKB). Gene-specific information Tables for CYP2C19. https:www.pharmgkb.org/page/cyp2c19 Ref Materials. Accessed May 21, 2025.

33. Zhao X, Zhang Z, Lu F, et al. Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis. Front Pharmacol. 2022 Oct 6;13:938419. doi: 10.3389/fphar.2022.938419.

34. Fu J, Sun CF, He HY, et al. The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitorscontaining regimens in Asian populations: a meta-analysis. Pharmacogenomics. 2021 Aug;22(13):859-879. doi: 10.2217/pgs-2020-0127.

35. Zihlif M, Bashaireh B, Rashid M, et al. Effect of major CYP2C19 genetic polymorphisms on Helicobacter pylori eradication based on different treatment regimens. Biomed Rep. 2022 Jan;16(1):2. doi: 10.3892/br.2021.1485.

36. Shah SC, Tepler A, Chung CP, et al. Host Genetic Determinants Associated With Helicobacter pylori Eradication Treatment Failure: A Systematic Review and Meta-analysis. Gastroenterology. 2021 Nov;161(5):1443-1459. doi: 10.1053/j.gastro.2021.07.043.

37. Scodellaro S, Bortolin KA, Marcon MA, et al. Optimizing proton-pump inhibitor therapy in paediatric eosinophilic esophagitis through CYP2C19 pharmacogenetic testing. J Can Assoc Gastroenterol. 2025 Mar 13;8(3):89-96. doi: 10.1093/jcag/gwaf003.

38. Yan L, Chen Y, Chen F, et al. Effect of Helicobacter pylori Eradication on Gastric Cancer Prevention: Updated Report From a Randomized Controlled Trial With 26.5 Years of Follow-up. Gastroenterology. 2022 Jul;163(1):154-162. e3. doi: 10.1053/j.gastro.2022.03.039.

39. Ferraz AML, Bandarra S, Mascarenhas P, et al. Characterization of CYP2C19*17 Polymorphism in a Portuguese Population Sample Relevant for Proton Pump Inhibitor Therapy—A Pilot Study. Med. Sci. Forum. 2021;5(1):19. doi: 10.3390/msf2021005019.

40. Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther. 2011 May;89(5):662-73. doi: 10.1038/clpt.2011.34.