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Karbalaei M, Yamaoka Y, Keikha M. Clinical significance of genetic polymorphisms of interleukin-1β and cytochrome P450 2C19 on the eradication of Helicobacter pylori. New Microbes New Infect 2023; 53:101131. [PMID: 37197056 PMCID: PMC10183653 DOI: 10.1016/j.nmni.2023.101131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 05/19/2023] Open
Affiliation(s)
- Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Yoshio Yamaoka
- Oita University Faculty of Medicine, Yufu, Oita, Japan
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Masoud Keikha
- Department of Microbiology and Virology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
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Zhao X, Zhang Z, Lu F, Xiong M, Jiang L, Tang K, Fu M, Wu Y, He B. 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; 13:938419. [PMID: 36278195 PMCID: PMC9582748 DOI: 10.3389/fphar.2022.938419] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 09/12/2022] [Indexed: 11/28/2022] Open
Abstract
Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis. Materials and methods: The literature was searched with the key words “H. pylori” and “CYP2C19” in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16. Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47–0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59–0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%). Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.
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Affiliation(s)
- Xianghong Zhao
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhongqiu Zhang
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Fang Lu
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Mengqiu Xiong
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liping Jiang
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ke Tang
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Min Fu
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yu Wu
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- H. pylori Research Key Laboratory, Nanjing Medical University, Nanjing, China
- *Correspondence: Bangshun He,
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Ghazvini K, Kamali H, Hosseininasab-nodoushan SA, Keikha M. The CYP2C19 polymorphisms effects on H. pylori cure rate in proton pump inhibitor-based therapeutic regimens: An updated meta-analysis. GENE REPORTS 2021; 25:101340. [DOI: 10.1016/j.genrep.2021.101340] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Shah SC, Tepler A, Chung CP, Suarez G, Peek RM, Hung A, Roumie C, Narula N. Host Genetic Determinants Associated With Helicobacter pylori Eradication Treatment Failure: A Systematic Review and Meta-analysis. Gastroenterology 2021; 161:1443-1459. [PMID: 34358488 PMCID: PMC8545829 DOI: 10.1053/j.gastro.2021.07.043] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 07/19/2021] [Accepted: 07/24/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Helicobacter pylori infects approximately 50% of individuals worldwide. Successful H pylori eradication is associated with reduced risk of gastric cancer and peptic ulcer disease, among other conditions. We hypothesized that host genetic determinants, especially those affecting gastric pH, might contribute to eradication therapy failure, particularly when treatment adherence and antibiotic susceptibility are confirmed. We aimed to conduct a meta-analysis of host genetic variants associated with H pylori eradication failure. METHODS We searched the literature for studies comparing posttreatment H pylori eradication failure vs success (outcome) according to host genetic polymorphisms (exposure). Reference groups were defined according to genotypes (or corresponding phenotypes) hypothesized to be associated with successful eradication. We pooled estimates using a random-effects model and performed comprehensive sensitivity analyses. RESULTS We analyzed 57 studies from 11 countries; the vast majority analyzed CYP2C19 polymorphisms. Among individuals prescribed eradication regimens with proton pump inhibitors predominantly CYP2C19 metabolized, enhanced vs poor metabolizer phenotypes were associated with a 2.52-fold significantly higher likelihood of eradication failure and 4.44-fold significantly higher likelihood when treatment adherence and H pylori clarithromycin susceptibility (if relevant) were confirmed. There was no association between CYP2C19 variants and eradication failure if proton pump inhibitors less metabolized by or that bypass CYP2C19 metabolism were used. IL1B polymorphisms that are vs are not associated with less gastric acid suppression were associated with 1.72-fold significantly higher likelihood of eradication failure. There was no association between MDR1 polymorphisms and H pylori eradication failure. The certainty of evidence was moderate. CONCLUSION Based on meta-analysis, we identified host genetic polymorphisms significantly associated with H pylori eradication failure; host genetics might underlie eradication failure among treatment-adherent individuals with confirmed H pylori antibiotic susceptibility.
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Affiliation(s)
- Shailja C. Shah
- Section of Gastroenterology, Veterans Affairs San Diego Health System (La Jolla, CA) and Tennessee Valley Healthcare System (Nashville, TN),Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville TN,Division of Gastroenterology, University of California, San Diego, La Jolla, CA,Corresponding Author Shailja C. Shah, MD MPH, 3550 La Jolla Village Drive, 3rd Floor, GI Section, VA San Diego Healthcare System, San Diego, CA 92161 USA, , Ph: 619-854-9550
| | - Adam Tepler
- Department of Medicine, New York University, New York, NY
| | - Cecilia P. Chung
- Division of Rheumatology, Vanderbilt University Medical Center, Nashville, TN,Section of Rheumatology, Veterans Affairs Tennessee Valley Healthcare System
| | - Giovanni Suarez
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville TN
| | - Richard M. Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville TN
| | - Adriana Hung
- Department of Medicine, Vanderbilt University Medical Center, Nashville TN,Section of Nephrology, Veterans Affairs Tennessee Valley Healthcare System
| | - Christianne Roumie
- Department of Medicine, Vanderbilt University Medical Center, Nashville TN,Department of Veterans Affairs, Medical Service and Geriatric Research and Education Clinical Center (GRECC) Tennessee Valley Healthcare System, Nashville, TN
| | - Neeraj Narula
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton Ontario Canada
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Zhang Y, Chen Y, Li B, Ding P, Jin D, Hou S, Cai X, Sheng X. The effect of monotropein on alleviating cisplatin-induced acute kidney injury by inhibiting oxidative damage, inflammation and apoptosis. Biomed Pharmacother 2020; 129:110408. [PMID: 32574971 DOI: 10.1016/j.biopha.2020.110408] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/10/2020] [Accepted: 06/13/2020] [Indexed: 12/15/2022] Open
Abstract
Although cisplatin is a common drug in the treatment of malignant tumors, its clinical application is limited due to various side effects, especially acute kidney injury (AKI). Till now, few effective pharmacological strategies can be applied to inhibit cisplatin-induced AKI. Here, we aimed to investigate the protective effects and possible mechanisms of monotropein on cisplatin-induced AKI. In this study, an AKI model was established in cisplatin-treated mice, and serum level of inflammatory cytokines, protein expressions of biochemical indicators and renal pathology were analyzed. Our results showed that our results showed that monotropein could significantly attenuate cisplatin-induced nephrotoxicity and reduce the levels of blood urea nitrogen (BUN) and serum creatinine (CRE). Furthermore, monotropein inhibited cisplatin-induced oxidative stress by reducing MDA level and increasing the activities of GSH, SOD and CAT. The underlying mechanisms of monotropein on alleviating cisplatin-induced AKI were associated with the activation of Nrf2/HO-1 pathway against oxidative stress and the inhibition on NF-κB signaling to suppress inflammation as well as the regulation on the expressions of proteins in apoptosis pathway in this renal injury model. This study firstly provided the evidence that monotropein could significantly attenuate cisplatin-induced AKI and suggested that monotropein might be used as a potential agent to alleviate side effects of cisplatin.
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Affiliation(s)
- Yuping Zhang
- Department of Gynaecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China
| | - Yonger Chen
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China
| | - Baixue Li
- Department of Gynaecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China
| | - Ping Ding
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China
| | - Daxiang Jin
- Department of Osteology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China
| | - Shaozhen Hou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China
| | - Xiaochun Cai
- Department of Gynecology and Obstetrics, Chenghai District People's Hospital, Shantou, 515800, Guangdong, China.
| | - Xiujie Sheng
- Department of Gynaecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
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Xing JJ, Hou JG, Liu Y, Zhang RB, Jiang S, Ren S, Wang YP, Shen Q, Li W, Li XD, Wang Z. Supplementation of Saponins from Leaves of Panax quinquefolius Mitigates Cisplatin-Evoked Cardiotoxicity via Inhibiting Oxidative Stress-Associated Inflammation and Apoptosis in Mice. Antioxidants (Basel) 2019; 8:antiox8090347. [PMID: 31480577 PMCID: PMC6769973 DOI: 10.3390/antiox8090347] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/23/2019] [Accepted: 07/24/2019] [Indexed: 12/13/2022] Open
Abstract
Background: Although kidney injury caused by cisplatin has attracted much attention, cisplatin-induced cardiotoxicity is elusive. Our previous studies have confirmed that saponins (ginsenosides) from Panax quinquefolius can effectively reduce acute renal injuries. Our current study aimed to identify the potential effects of saponins from leaves of P. quinquefolius (PQS) on cisplatin-evoked cardiotoxicity. Methods: Mice were intragastrically with PQS at the doses of 125 and 250 mg/kg daily for 15 days. The mice in cisplatin group and PQS + cisplatin groups received four times intraperitoneal injections of cisplatin (3 mg/kg) two days at a time from the 7th day, respectively. All mice were killed at 48 h following final cisplatin injection. Body weights, blood and organic samples were collected immediately. Results: Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with obvious histopathological changes and elevation of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT) concentrations and viabilities in serum. Cisplatin also impaired antioxidative defense system in heart tissues manifested by a remarkable reduction in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, demonstrating the overproduction of reactive oxygen species (ROS) and oxidative stress. Interestingly, PQS (125 and 250 mg/kg) can attenuate cisplatin-evoked changes in the above-mentioned parameters. Additionally, PQS administration significantly alleviated the oxidation resulted from inflammatory responses and apoptosis in cardiac tissues via inhibition of overexpressions of TNF-α, IL-1β, Bax, and Bad as well as the caspase family members like caspase-3, and 8, respectively. Conclusion: Findings from our present research clearly indicated that PQS exerted significant effects on cisplatin-induced cardiotoxicity in part by inhibition of the NF-κB activity and regulation of PI3K/Akt/apoptosis mediated signaling pathways.
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Affiliation(s)
- Jing-Jing Xing
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Jin-Gang Hou
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- Intelligent Synthetic Biology Center, Daejeon 34141, Korea
| | - Ying Liu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- College of Life Science, Kyung Hee University, Seoul 446-701, Korea
| | - Ruo-Bing Zhang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Shuang Jiang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Shen Ren
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Ying-Ping Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Qiong Shen
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Wei Li
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China
| | - Xin-Dian Li
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
| | - Zi Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
- National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.
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CYP2C19*2 polymorphism in Polish peptic ulcer patients. Pharmacol Rep 2019; 71:272-275. [DOI: 10.1016/j.pharep.2018.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 11/28/2018] [Accepted: 12/21/2018] [Indexed: 12/14/2022]
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Rech TF, Mazzoleni LE, Mazzoleni F, Francesconi CFDM, Sander GB, Michita RT, Nabinger DD, Milbradt TC, Torresini RJS, Simon D. Helicobacter pylori eradication: influence of interleukin-1beta -31 C/T polymorphism. Braz J Infect Dis 2018; 22:311-316. [PMID: 30048609 PMCID: PMC9428014 DOI: 10.1016/j.bjid.2018.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 06/22/2018] [Accepted: 06/26/2018] [Indexed: 12/16/2022] Open
Abstract
Aim To analyze the influence of the –31 C/T polymorphism of the interleukin-1β gene on Helicobacter pylori eradication therapy success in patients with functional dyspepsia. Methods Functional dyspepsia was diagnosed according to the Rome III criteria. All patients underwent upper gastrointestinal endoscopy, and gastric biopsies were obtained at screening and 12 months after randomization (last follow-up visit). Urease test and histological examination were performed to define the H. pylori status. Patients received twice-daily amoxicillin, clarithromycin and omeprazole for 10 days. Genotyping of the interleukin-1beta –31 C/T polymorphism (rs1143627) was performed using polymerase chain reaction-restriction fragment length polymorphism. Results One hundred forty-nine patients received treatment with triple therapy for H. pylori eradication. Only one patient was lost to follow-up, and adherence to study medication was 94.6%. A total of 148 patients (mean age 46.08 ± 12.24 years; 81.8% women) were evaluated for the influence of the interleukin-1beta –31 C/T polymorphism on the outcome of H. pylori eradication therapy. After treatment, bacteria were eradicated in 87% of patients (129/148). Genotype frequencies of the polymorphism were as follows: CC, 38/148 (25.7%); CT, 71/148 (47.9%); and TT, 39/148 (26.4%). Successful eradication rate was 78.9%, 94.4% and 82.1% for the CC, CT and TT genotypes, respectively. The CT genotype was significantly associated with successful H. pylori eradication (p = 0.039). Conclusion This study suggests that the CT genotype of the interleukin-1beta –31 C/T polymorphism plays a role in the successful eradication of H. pylori among patients with functional dyspepsia.
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Affiliation(s)
- Tássia Flores Rech
- Universidade Luterana do Brasil, Laboratório de Genética Molecular Humana, Canoas, RS, Brazil
| | - Luiz Edmundo Mazzoleni
- Hospital de Clínicas de Porto Alegre, Serviço de Gastroenterologia, Porto Alegre, RS, Brazil
| | - Felipe Mazzoleni
- Hospital de Clínicas de Porto Alegre, Serviço de Gastroenterologia, Porto Alegre, RS, Brazil
| | | | - Guilherme Becker Sander
- Hospital de Clínicas de Porto Alegre, Serviço de Gastroenterologia, Porto Alegre, RS, Brazil
| | - Rafael Tomoya Michita
- Universidade Luterana do Brasil, Laboratório de Genética Molecular Humana, Canoas, RS, Brazil
| | - Débora Dreher Nabinger
- Universidade Luterana do Brasil, Laboratório de Genética Molecular Humana, Canoas, RS, Brazil
| | - Tobias Cancian Milbradt
- Hospital de Clínicas de Porto Alegre, Serviço de Gastroenterologia, Porto Alegre, RS, Brazil
| | | | - Daniel Simon
- Universidade Luterana do Brasil, Laboratório de Genética Molecular Humana, Canoas, RS, Brazil.
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Román M, Ochoa D, Sánchez-Rojas SD, Talegón M, Prieto-Pérez R, Rivas Â, Abad-Santos F, Cabaleiro T. Evaluation of the relationship between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, pantoprazole and rabeprazole. Pharmacogenomics 2015; 15:1893-901. [PMID: 25495411 DOI: 10.2217/pgs.14.141] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
AIM To evaluate the possible association between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, rabeprazole and pantoprazole. MATERIALS & METHODS 151 healthy volunteers were evaluated for polymorphisms in the CYP2C19 gene using real-time polymerase chain reaction. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. RESULTS Carriers of the *2 allele displayed poor metabolism for all the PPIs studied (around 50% decrease in clearance). Subjects with the *17 allele showed a light increase in clearance compared with *1/*1 (not significant). CONCLUSION CYP2C19*2 is associated with decreased clearance of all the PPIs, that could be associated with higher drug efficacy. CYP2C19*17 could increase clearance of these drugs, although the effect seems small.
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Affiliation(s)
- Manuel Román
- Service of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain
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Cure rate of Helicobacter pylori infection in Egyptian children related to CYP2C19 gene polymorphism. Indian J Gastroenterol 2014; 33:330-5. [PMID: 24610583 DOI: 10.1007/s12664-014-0450-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 02/13/2014] [Indexed: 02/04/2023]
Abstract
OBJECTIVES This study was done in order to investigate the effect of CYP2C19 genetic polymorphism on the cure rate of children who received proton pump inhibitors (PPI)-based triple therapy for treating Helicobacter pylori (H. pylori) infection. METHODS Participants included 100 children with H. pylori-positive gastritis diagnosed by endoscopy and biopsy in addition to H. pylori stool antigen test. Cure rate was assessed after 1 month of completion of a triple treatment course for 14 days. CYP2C19 polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS Results showed that cases with a CYP2C19 genotypic status consistent with the heterozygote extensive metabolizers (HetEMs) had a higher cure rate of H. pylori when compared with the homozygote extensive metabolizers (HomEMs) although it was statistically nonsignificant (84.6 vs. 69.2). In addition, the poor metabolizers (PMs) had a higher cure rate compared with those of the HomEMs which was also statistically nonsignificant (77.8 vs. 69.2). The cure rate was also higher among both the groups of HetEMs and PMs combined together compared to the HomEMs (OR = 2.15, p > 0.05). Comparing cases regarding their age, gender, and severity of H. pylori gastritis revealed a better cure rate in the age group >10 years, in females and in mild and moderate cases than other cases although statistically nonsignificant. CONCLUSION The higher cure rate of H. pylori infection using the triple therapy for 2 weeks among HetEMs and PMs cases compared to the HomEMs might warrant a need for a therapy augmentation or modification for the HomEMs.
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Zhao Y, Wang JW, Tanaka T, Hosono A, Ando R, Tokudome S, Soeripto, Triningsih FXE, Triono T, Sumoharjo S, Achwan EYWA, Gunawan S, Li YM. Association between TNF-α and IL-1β genotypes vs Helicobacter pylori infection in Indonesia. World J Gastroenterol 2013; 19:8758-8763. [PMID: 24379597 PMCID: PMC3870525 DOI: 10.3748/wjg.v19.i46.8758] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 10/22/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the correlation between the Helicobacter pylori (H. pylori) infection and host genetic background of healthy populations in Indonesia.
METHODS: In March 2007, epidemiological studies were undertaken on the general population of a city in Indonesia (Mataram, Lombok). The participants included 107 men and 187 women, whose ages ranged from 6 to 74 years old, with an average age of 34.0 (± 14.4) (± SD). The H. pylori of subject by UBT method determination, and through the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method parsing the single nucleotide polymorphism of interleukin (IL)-8, IL-4, IL-1β, CD14, tumor necrosis factor (TNF-α) and tyrosine-protein phosphates non-receptor type 11 (PTPN11) genotypes. The experimental data were analyzed by the statistical software SAS.
RESULTS: The H. pylori infection rates in the healthy Indonesian population studied were 8.4% for men and 12.8% for women; no obvious differences were noted for H. pylori infection rates by sex or age. TC genotypes of IL-4, TC and CC genotypes of TNF-α, and GA genotypes of PTPN11, were higher in frequency. Both CC and TC genotype of TNF-α T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of (OR = 1.99; 95%CI: 0.67-5.89) and (OR = 1.66; 95%CI: 0.73-3.76), respectively. C allele of IL-1β T-31C gene locus was at a higher risk (OR = 1.11; 95%CI: 0.70-1.73) of H. pylori infection, but no statistical significance was found in our study.
CONCLUSION: We reveal that the association between the TNF-α and IL-1β genotypes may be the susceptibility of H. pylori in the studied population.
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Preventive medical services not covered by public health insurance at Daiko Medical Center in Japan, 2004-2011. NAGOYA JOURNAL OF MEDICAL SCIENCE 2012; 74:115-21. [PMID: 22515117 PMCID: PMC4831256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Preventive medical services not covered by public health insurance started in the Daiko Medical Center of Nagoya University in June, 2004. Those services included: (1) Helicobacter pylori (H. pylori) diagnosis and eradication treatments, for which CYP2C19 genotyping was introduced in November 2005; (2) smoking cessation support with genotype tests of CYP1A1 Ile462Val, GSTM1 present/null, GSTT1 present/null, and NQO1 Pro187Ser; (3) advice on alcohol consumption with genotype tests of ADH Arg47His and ALDH2 Glu487Lys; (4) advice on folate-associated diseases with a genotype test of MTHFR C677T; (5) advice on a tumor marker CA19-9 with genotype tests of Lewis and Secretor genes; and (6) raloxifene prescription aimed to prevent breast cancer for high-risk postmenopausal women. A total of 683 patients visited the Center until it closed in March 2011. Those given diagnoses and eradication treatments for H. pylori numbered 567, followed by 44 for smoking cessation support, 35 for advice on folate-associated diseases, 26 for advice on alcohol consumption, 8 for CA19-9, and 3 for raloxifene prescription. Around 2004, public interest in H. pylori was relatively high, but thereafter patient numbers dropped markedly. The Center closed in March 2011 due to the reduction in patient visits. Our unique trial showed that continuing to provide uninsured preventive services at a clinic was difficult in Japan without the affiliation of hospitals/clinics providing medical services covered by public health insurance.
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Tamura T, Kurata M, Inoue S, Kondo T, Goto Y, Kamiya Y, Kawai S, Hamajima N. Improvements in Helicobacter pylori eradication rates through clinical CYP2C19 genotyping. NAGOYA JOURNAL OF MEDICAL SCIENCE 2011; 73:25-31. [PMID: 21614934 PMCID: PMC11254356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Lansoprazole (LPZ), amoxicillin (AMPC) and clarithromycin (CAM) are commonly used drugs (LAC regimen) for Helicobacter pylori (H. pylori) eradication, but the eradication rate with this regimen was reported to be 70% to 90%. A few studies have reported that a successful eradication was associated with the CYP2C19 genotype, which influences the metabolism of proton pump inhibitors (PPI) including LPZ. This study examined the changes in the H. pylori eradication rates between the periods before and after the commencement of a routine genetic test for CYP2C19 at the Daiko Medical Center in Nagoya, Japan, in November, 2005. Subjects were patients who visited the Center during the period from June, 2004 to August, 2010. The patients were classified into three groups according to their CYP2C19 genotype: rapid metabolizers (RM) with a *1*1 genotype, intermediate metabolizers (IM) with a *1*2 or *1*3 genotype, and poor metabolizers (PM) with a *2*2, *2*3, or *3*3 genotype. Non-rapid metabolizers (IM and PM) were basically treated with a LAC regimen, while RMs were treated with a RAM reg imen(rabeprazole, AMPC, and metronidazole). The eradication rate was 80.0% (n=90) for the period without the genetic testing and 88.7% (n=124) for the period with the genetic testing (chi2=3.11, p=0.078). The age-sex adjusted odds ratio of eradication success was 2.29 (95% confidence interval, 0.99-5.28, p=0.051) for the latter period relative to the former period among those less than 70 years of age. Those results suggested that the routine genetic test which allows a choice of the RAM regimen for R M improved the eradication rate.
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Affiliation(s)
- Takashi Tamura
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Japan.
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Abstract
During developmental age, differences in pharmacodynamic reactions to several drugs may reflect polymorphisms of genes encoding drug-transporting proteins, receptors, drug targets, and gene products, whose disturbed activity sometimes plays an important role in certain diseases. Administration of drugs with a narrow therapeutic index may quite easily be associated with changes in pharmacokinetics and development of adverse drug reactions, which occasionally may cause fatalities. In such cases, polypragmasy and resulting drug interactions may enhance effects of changes in drug-metabolizing enzymes' activities. Phenotyping and genotyping of patients slowly are finding their place in some therapeutic regimens used in clinical gastroenterology and hepatology. At present, some assays to measure, for example, thiopurine S-methyltransferase activity are already commercially available. Polymorphisms of CYP450 enzymes, interleukins, and altered gene expression play an important role in some patients' various gastrointestinal tract and liver diseases. Herbal drugs also affect proinflammatory and antiinflammatory cytokine and nitric oxide balance in the body. Therapeutic use of recombined proteins, such as infliximab, natalizumab, onercept, humanized antibody to integrin α-4 β-7, or IFN-β in some large-bowel diseases increased therapeutic efficacy. IFN-α used in the patients with chronic hepatitis C improved cellular immunity in these subjects and exerted antiviral activity. Practical application of progress in pharmacogenetics, pharmacokinetics, pharmacodynamics, and use of bioproducts in novel therapeutic regimens has opened therapeutic frontiers and increased clinical safety.
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Affiliation(s)
- Joseph Prandota
- Department of Social Pediatrics, Faculty of Health Sciences, University School of Medicine, Wroclaw, Poland.
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Sugimoto M, Furuta T, Yamaoka Y. Influence of inflammatory cytokine polymorphisms on eradication rates of Helicobacter pylori. J Gastroenterol Hepatol 2009; 24:1725-1732. [PMID: 20136959 PMCID: PMC3128255 DOI: 10.1111/j.1440-1746.2009.06047.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pro-inflammatory cytokines and anti-inflammatory cytokines are produced in gastric mucosa from inflammatory cells activated by Helicobacter pylori (H. pylori) infection. Of the inflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha have a potent inhibitive effect on gastric acid production. Polymorphisms in these genes are associated with individual differences in cytokine messenger RNA levels, which result in different gastric mucosal inflammation, different acid inhibition and different gastroduodenal disease risks in response to H. pylori infection. The sustained higher intragastric pH during an eradication therapy is known to be one of the therapeutic determinants of the H. pylori eradication as well as antibiotics resistance and poor compliance. The IL-1B-511 polymorphism is related to eradication rate, and, in combined analysis of previous reports, the eradication rate in patients with the IL-1B-511 C/C genotype (77.4%, 209/270), low IL-1beta producer genotype, is lower than that of the IL-1B-511 C/T and T/T genotypes (87.2%, 631/724) (Odds ratio for eradication failure: 1.98, 95% confidence interval: 1.38-2.84, P = 0.0002). Moreover, the odds ratio of combined CYP2C19 rapid metabolizer-IL-1B-511 C/C type for eradication failure is 11.15 (5.23-23.78) times that of the CYP2C19 poor metabolizer-IL-1B-511 non-C/C type. However, there is no positive data indicating the role of other inflammatory cytokine polymorphisms (e.g. IL-1RN, TNF-A or IL-10) in eradication therapy. Nevertheless, the studies show that inflammatory cytokine polymorphisms, especially the IL-1B-511 T/T genotype, are the determinants of eradication by affecting gastric acid secretion and mucosal inflammation. Therefore, the tailored eradication therapy, considering inflammatory cytokine polymorphisms, may be effective for the higher eradication rates.
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Affiliation(s)
- Mitsushige Sugimoto
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA.
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Associations of plasma IL-8 levels withHelicobacter pyloriseropositivity, gastric atrophy, andIL-8T-251A genotypes. Epidemiol Infect 2009; 138:512-8. [PMID: 19719901 DOI: 10.1017/s0950268809990677] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
SUMMARYThere are few data on circulatory pro-inflammatory cytokine levels and cytokine gene polymorphisms inH. pylori-positive patients. A cross-sectional study was conducted to examine the effects ofH. pyloriinfection, gastric atrophy, and theIL-8T-251A polymorphism on plasma IL-8 levels in 98 Japanese adults. Seventy-one subjects were positive forH. pyloriinfection. The geometric mean of plasma IL-8 concentration was significantly higher in subjects withH. pyloriinfection than in those without (P=0·001). The development of atrophy was negatively associated with IL-8 levels in theH. pylori-positive subjects, although not significantly. Plasma IL-8 levels in the T/T genotype were associated withH. pyloriinfection and atrophy status (P=0·016). Our findings suggested that circulating IL-8 levels were associated withH. pyloriinfection. The effect ofH. pyloriinfection on plasma IL-8 levels was not clearly modified by theIL-8T-251A polymorphism.
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Sugimoto M, Yamaoka Y. Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy. Arch Immunol Ther Exp (Warsz) 2009; 57:45-56. [PMID: 19219527 PMCID: PMC3118989 DOI: 10.1007/s00005-009-0007-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2008] [Accepted: 10/20/2008] [Indexed: 12/11/2022]
Abstract
The cure rates of Helicobacter pylori infection by using a combination of a proton pump inhibitor (PPI) and antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of acid inhibition during the treatment. Currently used empirical triple therapies do not reliably produce a > or =80% cure rate on an intention-to-treat basis. Therefore, tailored regimens based on relevant microbiological findings and pharmacogenomics are recommended for attaining an acceptable > or =95% cure rate. Recently, virulence factors of H. pylori, such as cagA and vacA, are reported to be major factors determining the cure rates. Individuals infected with strains with cagA-negative and vacA s2 genotypes have significantly increased risk of eradication failure of H. pylori infection. These virulence factors enhance gastric mucosal inflammation and are associated with the development of peptic ulcer and gastric cancer. H. pylori virulence factors induce proinflammatory cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor (TNF)- which influence mucosal inflammation and/or gastric acid secretion. When physicians select an H. pylori eradication regimen with an acceptable cure rate, they might need to consider H. pylori virulence factors, especially cagA and vacA.
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Affiliation(s)
- Mitsushige Sugimoto
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
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Sugimoto M, Furuta T, Shirai N, Kodaira C, Nishino M, Yamade M, Ikuma M, Watanabe H, Ohashi K, Hishida A, Ishizaki T. Treatment strategy to eradicate Helicobacter pylori infection: impact of pharmacogenomics-based acid inhibition regimen and alternative antibiotics. Expert Opin Pharmacother 2007; 8:2701-2717. [PMID: 17956193 DOI: 10.1517/14656566.8.16.2701] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1 beta). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.
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Affiliation(s)
- Mitsushige Sugimoto
- Hamamatsu University School of Medicine, First Department of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
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Elmaagacli AH, Koldehoff M, Steckel NK, Trenschel R, Ottinger H, Beelen DW. Cytochrome P450 2C19 loss-of-function polymorphism is associated with an increased treatment-related mortality in patients undergoing allogeneic transplantation. Bone Marrow Transplant 2007; 40:659-64. [PMID: 17680025 DOI: 10.1038/sj.bmt.1705786] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The polymorphic gene expression of CYP2C19 causes individual variability in drug metabolism and thereby in pharmacologic and toxicologic responses. We genotyped 286 patients and their donors for the CYP2C19 gene who underwent allogeneic transplantation for various diseases and analyzed their outcome. Patients were classified as: poor metabolizers (PMs; 3.1%), intermediate metabolizers (IMs; 24.5%) and extensive metabolizers (EMs; 72.5%). Patients genotyped as PMs had significant higher hepato- and nephrotoxicities compared to IMs or EMs. Maximum bilirubin and serum creatinine levels measured after transplant were approximately twofold higher than those of EMs or IMs. The increased toxicity resulted in an increased 4-year estimate for transplant-related mortality (TRM) with 50+/-18.6% for PMs compared to 25.1+/-3.7% for EMs (P<0.018) and 22.7 +/-5.6% for IMs (P<0.042), whereas no significant influence for relapse rate, overall survival or incidence of acute graft-versus-host disease grade 2-4 were found between the groups. Multivariate analysis including all potential factors that might influence TRM confirmed that the genotype of CYP2C19 is an independent factor, which influenced TRM significantly. These results suggest that genotyping for CYP450 2C19 can help to identify patients with higher risk for TRM.
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Affiliation(s)
- A H Elmaagacli
- Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany.
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