title: Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: a meta-analysis of randomized clinical trials.
abstract: BACKGROUND
  There are inconsistent conclusions about whether CYP2C19 variants could affect H. pylori eradication rate in patients treated with the proton pump inhibitor (PPI)-based therapy. We therefore performed a meta-analysis of randomized clinical trials (RCTs) to re-evaluate the impact of CYP2C19 variants on PPI-based triple therapy for the above indication.
  
  
  METHODS
  All relevant RCTs in the PubMed, Cochrane Library, EMBASE, Web of Science and two Chinese databases (up to February 2013) were systematically searched, and a pooled analysis was performed with the odds ratio (OR) and 95% confidence interval (CI) by the STATA software.
  
  
  RESULTS
  Sixteen RCT datasets derived from 3680 patients were included. There was no significant heterogeneity across the data available in this meta-analysis. There were significant differences in that rate between homozygous (HomEMs) and heterozygous (HetEMs) extensive metabolizers (OR 0.724; 95% CI 0.594-0.881), between HomEMs and poor metabolizers (PM) (OR 0.507; 95%CI 0.379-0.679), or between HetEMs and PMs (OR 0.688; 95%CI 0.515-0.920), regardless of the PPI being taken. Furthermore, sub-analysis of individual PPIs was carried out to explore the difference across all the PPIs used. A significantly low rate was seen in HomEMs vs. HetEMs taking either omeprazole (OR 0.329; 95%CI 0.195-0.553) or lansoprazole (OR 0.692; 95%CI 0.485-0.988), and also in HomEMs vs. PMs for omeprazole (OR 0.232; 95%CI 0.105-0.515) or lansoprazole (OR 0.441; 95%CI 0.252-0.771). However, there was no significant difference between HetEMs and PMs taking either one. No significant differences were observed for rabeprazole or esomeprazole across the CYP2C19 genotypes of interest.
  
  
  CONCLUSIONS
  Carriage of CYP2C19 loss-of-function variants is associated with increased H. pylori eradication rate in patients taking PPI-based triple therapies when omeprazole or lansoprazole is chosen. However, there is no a class effect after use of rabeprazole or esomeprazole.
authors: Department of Pharmacy, Peking University Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University Third Hospital, Beijing, China.
authors: Hui-Lin
authors: HL
authors: Tang
authors: Yan
authors: Y
authors: Li
authors: Yong-Fang
authors: YF
authors: Hu
authors: Hong-Guang
authors: HG
authors: Xie
authors: Suo-Di
authors: SD
authors: Zhai
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D004359:Drug Therapy, Combination; D014644:Genetic Variation; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D016017:Odds Ratio; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
references: Pharmacogenomics. 2011 Jun;12(6):873-88
references: 21692617
references: Gut Liver. 2010 Jun;4(2):201-6
references: 20559522
references: Aliment Pharmacol Ther. 1999 Aug;13(8):1047-55
references: 10468680
references: Expert Opin Drug Saf. 2009 Jan;8(1):119-26
references: 19236223
references: Eur J Gastroenterol Hepatol. 2003 Jan;15(1):27-33
references: 12544691
references: J Gastroenterol Hepatol. 2002 Jul;17(7):748-53
references: 12121503
references: Pharmacogenomics J. 2008 Feb;8(1):4-15
references: 17549068
references: Clin Pharmacol Ther. 1997 Aug;62(2):129-37
references: 9284848
references: J Antimicrob Chemother. 1997 Jan;39(1):5-12
references: 9044021
references: Lancet. 1997 Jan 25;349(9047):265-9
references: 9014926
references: N Engl J Med. 2001 Sep 13;345(11):784-9
references: 11556297
references: Aliment Pharmacol Ther. 2005 Feb 15;21(4):491-7
references: 15710002
references: J Clin Pharm Ther. 2010 Dec;35(6):713-22
references: 21054464
references: J Gastroenterol Hepatol. 2005 Dec;20 Suppl:S22-8
references: 16359346
references: Aliment Pharmacol Ther. 2005 Feb 1;21(3):283-8
references: 15691303
references: Aliment Pharmacol Ther. 2012 Sep;36(5):414-25
references: 22803691
references: CMAJ. 2007 Apr 10;176(8):1091-6
references: 17420491
references: Aliment Pharmacol Ther. 2003 Jan;17(2):259-64
references: 12534411
references: Eur J Clin Pharmacol. 2010 Jul;66(7):681-7
references: 20376628
references: Med Clin North Am. 2005 Mar;89(2):313-44, viii
references: 15656929
references: Dig Liver Dis. 2001 Nov;33(8):671-5
references: 11785712
references: PLoS Med. 2009 Jul 21;6(7):e1000097
references: 19621072
references: Nihon Rinsho. 2004 Mar;62(3):455-8
references: 15038086
references: Gastroenterology. 1996 Aug;111(2):358-67
references: 8690200
references: Aliment Pharmacol Ther. 2007 May 1;25(9):1105-13
references: 17439512
references: Lancet. 1984 Jun 16;1(8390):1311-5
references: 6145023
references: Aliment Pharmacol Ther. 1999 Aug;13 Suppl 3:27-36
references: 10491726
references: Helicobacter. 2007 Oct;12 Suppl 1:31-7
references: 17727458
references: Helicobacter. 2008 Dec;13(6):532-41
references: 19166419
references: Dig Dis Sci. 2001 Nov;46(11):2445-50
references: 11713950
references: Lancet. 1988 Dec 24-31;2(8626-8627):1437-42
references: 2904568
references: J Gastroenterol Hepatol. 1997 Jul;12(7):473-80
references: 9257236
references: Clin Pharmacol Ther. 2007 Apr;81(4):521-8
references: 17215846
references: Zhonghua Nei Ke Za Zhi. 2004 Jan;43(1):13-5
references: 14990013
references: Clin Pharmacol Ther. 1999 May;65(5):552-61
references: 10340921
references: Aliment Pharmacol Ther. 2001 Sep;15(9):1479-84
references: 11552922
references: Clin Ther. 2010 Nov;32(12):2003-11
references: 21118735
references: Ther Drug Monit. 1990 Jul;12(4):415-6
references: 2396316
references: Nature. 2000 Mar 23;404(6776):398-402
references: 10746728
references: JAMA. 1994 Jul 6;272(1):65-9
references: 8007082
references: Gut. 2007 Jun;56(6):772-81
references: 17170018
references: Helicobacter. 2003 Apr;8(2):111-9
references: 12662378
references: Am J Gastroenterol. 2003 Nov;98(11):2403-8
references: 14638340
references: Am J Gastroenterol. 2007 Aug;102(8):1808-25
references: 17608775
references: Am J Gastroenterol. 2006 Jul;101(7):1467-75
references: 16863547
references: Aliment Pharmacol Ther. 2003 Feb;17 Suppl 1:5-9
references: 12614299