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World J Gastroenterol. Nov 21, 2014; 20(43): 16029-16036
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16029
CYP2C19 polymorphism influences Helicobacter pylori eradication
Chao-Hung Kuo, Chien-Yu Lu, Hsiang-Yao Shih, Chung-Jung Liu, Meng-Chieh Wu, Huang-Ming Hu, Wen-Hung Hsu, Fang-Jung Yu, Deng-Chyang Wu, Fu-Chen Kuo
Chao-Hung Kuo, Chien-Yu Lu, Hsiang-Yao Shih, Chung-Jung Liu, Meng-Chieh Wu, Huang-Ming Hu, Wen-Hung Hsu, Fang-Jung Yu, Deng-Chyang Wu, Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Chao-Hung Kuo, Chien-Yu Lu, Huang-Ming Hu, Wen-Hung Hsu, Fang-Jung Yu, Deng-Chyang Wu, Department of Medicine, Faculty of Medicine, College of Medicine and Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Hsiang-Yao Shih, Meng-Chieh Wu, Deng-Chyang Wu, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
Fu-Chen Kuo, Graduate Institute of Public Health, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Fu-Chen Kuo, School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan
Author contributions: Kuo CH wrote this manuscript; Lu CY, Shih HY, Liu CJ, Wu MC, Hu HM, Hsu WH and Yu FJ designed research; Wu DC and Kuo FC polished the paper.
Supported by Kaohsiung Medical University “Aim for the Top Universities Grant, grant No. KMU-TP103G01 and No. KMU-TP103 G04 (partially)
Correspondence to: Fu-Chen Kuo, PhD, School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, No.1, Yida Rd., Yanchao Shiang, Kaohsiung 824, Taiwan. fuchenkuotw@yahoo.com.tw
Telephone: +886-7-73135612 Fax: +886-7-73135612
Received: February 21, 2014
Revised: July 4, 2014
Accepted: August 13, 2014
Published online: November 21, 2014
Abstract

The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration.

Keywords: Helicobacter pylori, CYP2C19, Polymorphism, Eradication, Rabeprazole, Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole

Core tip: This manuscript outlines the impact of cytochrome P450 2C19 (CYP2C19) polymorphism on eradication of Helicobacter pylori (H. pylori), including the influences on first line triple therapies, rescue therapies and levofloxacin- based therapies. We suggest that the strategy of eradicating H. pylori should include the examination of CYP2C19 polymorphism, especially for patients receiving rescue therapies or with drug resistances.