EFF ECT OF CYP2C19 GENETIC POLYMORPHISMS ON THE EFFI CACY OF PROTON PUMP INHIBITOR-BASED TRIPLE ERADICATION THERAPY IN SLAVIC PATIENTS WITH PEPTIC ULCERS: A META-ANALYSIS

Introduction. Several meta-analyzes reported the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication. Most of the studies which were included in these meta-analyzes were held on Asian population. Thus, there is lack of information about the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients with peptic ulcers. The aim of the study - to determine whether СYP2C19 affect the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients with peptic ulcers. Methods. Data search was performed using Russian index of scientific citation database, Google Scholar and MEDLINE PubMed. Statistics was held in Review Manager v 5.3. The odds ratio (OR) and 95% confidence interval (95% CI) for eradication of H.pylori was estimated in a fixed-effect model when no heterogeneity across the studies was indicated. Results. Four articles published between 2008 and 2015 were included in meta-analysis (three Russian studies, one Polish study). Eradication rates were significantly lower in CYP2C19 extensive metabolizers of proton pump inhibitors than in a combined group of intermediate and poor metabolizers (OR = 1,90, CI-95% 1,08-3,34, p = 0,03; heterogeneity: I2= 0%, p = = 0,74). We also found that proton pump inhibitor-based triple eradication therapy achieved higher rates in poor metabolizers than in a combined group of intermediate and extensive metabolizers of CYP2C19 (OR= 5,48 CI-95% 1,51-19,93, р = = 0,01; heterogeneity: I2= 0%, p = 0,66). Conclusion. The impact of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients appears significant.

CYP2C19, Helicobacter pylori, CYP2C19, cytochrome P450, pharmacogenetics, eradication, Helicobacter pylori, meta-analysis, proton pump inhibitor, peptic ulcer, Slavs, Caucasians

1. Маев И. В. Современные представления о заболеваниях желудочно-кишечного тракта, ассоциированных с Helicobacter pylori. Терапевтический архив. 2006; 78(2):10-5.

2. Исаков В. А. Диагностика и лечение инфекции, вызванной Helicobacter pylori: IV Маастрихтское соглашение / Новые рекомендации по диагностике и лечению инфекции H. pylori - Маастрихт IV (Флоренция). Best Clinical Practice. Русское издание. 2012. Вып.2. С. 4-23.

3. Malfertheiner, P., Megraud, F., O`Morain, C., et al. Management of Helicobacter pylori infection - the Maastricht IV/ Florence Consensus Report. Gut 2012; 61(5):646-64.

4. Ивашкин В. Т., Маев И. В., Лапина Т. Л., Шептулин А. А. и комитет экспертов. Рекомендации Российской Гастроэнтерологической Ассоциации по диагностике и лечению инфекции Helicobacter pylori у взрослых. Рос журн гастроэнт гепатол колопроктол 2012; 22(1):87-9.

5. Graham D. Y., Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance / Gut. - 2010. - Vol. 59. - P. 1143-1153.

6. Маев И. В., Кучерявый Ю. А., Андреев Д. Н. Причины неэффективности антигеликобактерной терапии // РЖГГК. 2013. № 6. С. 62-72.

7. De Morais S. M. et al. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol. 1994. 46(4): 594-8.

8. Sim S., Risinger C., Dahl M. L. et al. Сommon 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): 103-113.

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

10. Zhao F, Wang J, Yang Y, Wang X, Shi R, Xu Z, Huang Z, Zhang G. Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis.Helicobacter. 2008;13(6):532-41.

11. Padol S., Yuan Y.H., Thabane M., Padol I.T., Hunt R.H. The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple fist-line PPI therapies: a meta-analysis. Am J Gastoenterol 2006;101:1467-75.

12. McNicholl A.G., Linares P.M., Nyssen O.P., Calvet X., Gisbert J.P. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2012;36(5):414-25.

13. McNicholl A.G., Linares P.M., Nyssen O.P., Calvet X., Gisbert J.P. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection.Aliment Pharmacol Ther. 2012;36(5):414-25.

14. Елохина Е. В., Костенко М. Б., Ливзан М. А., Скальский С. В. Эффективность эрадикационной терапии у пациентов с язвенной болезнью, ассоциированной с Helicobacter pylori, в зависимости от генотипа лекарственного метаболизма ингибиторов протонной помпы. Экспериментальная и клиническая гастроэнтерология. 2015; № 3 (115): 31-33.

15. Оганесян Т. С. Значение полиморфизма генов цитохрома-P4502C19 и интерлейкина-1β для прогноза эффективности эрадикационной терапии язвенной болезни желудка и двенадцатиперстной кишки, ассоциированной с Helicobacter pylori. Автореферат диссертации на соискание ученой степени кандидата медицинских наук / Московский государственный медико-стоматологический университет. Москва, 2008.

16. Корнюков Г. В. Фармакогенетичекие особенности эрадикационной терапии у больных язвенной болезнью двенадцатиперстной кишки. Автореферат диссертации на соискание ученой степени кандидата медицинских наук / Институт повышения квалификации специалистов здравоохранения МЗ Хабаровского края. Москва, 2008.

17. Gawrońska-Szklarz B, Siuda A, Kurzawski M, Bielicki D, Marlicz W, Droździk M. Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pyloriinfection by triple therapy with pantoprazole, amoxicillin, and metronidazole. Eur J Clin Pharmacol. 2010; 66(7): 681-7.

18. Furuta T, Sugimoto M, Shirai N, Ishizaki T. CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor. Pharmacogenomics. 2007; 8(9):1199-210.