Effect of the CYP2C19 Polymorphism in Helicobacter Pylori Eradication

Summary

Background: Triple therapy efficacy against Helicobacter pylori is low worldwide, thus alternatives must be sought to improve eradication. Aim: To determine CYP2C19 genetic polymorphism effect on H. pylori eradication. Methods: A randomized single blinded clinical trial including 133 patients was carried-out. H. pylori infection was confirmed by histology and microbiological test. Antibiotic susceptibility to amoxicillin and clarithromycin was performed to avoid confusion bias in analysis results. CYP2C19 polymorphism "asterisk" \*1, "asterisk"\*2 and "asterisk" \*3 was analyzed by Real time PCR (Roche ®), and nested PCR for CYP2C19 "asterisk" \*17 polymorphism. Participants were randomized into two groups for different H. pylori therapies, one with standard omeprazole doses and another with omeprazole doses depending on CYP2C19 polymorphism. H. pylori eradicating was verified by stool antigen testing (Meridian ®). The general results was analysis by statistical computer program and the effectiveness of each therapy was analyzed by intention to treat (ITT) and by protocol (PP). The study allowed to know the prevalence of the main polymorphisms of CYP2C19 in Bogotá-Colombia, also allowed to know the effectivenesses of the two therapies evaluated for H. pylori infection. Additionally, the importance of personalized medicine in H. pylori eradication therapy was known.

Timeline

Start

2012-09-10

Primary completion

2015-08-08

Completion

2015-08-08

Publications

• Background Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008 Jun;5(6):321-31. doi: 10.1038/ncpgasthep1138. Epub 2008 Apr 29.
• Background Sapone A, Vaira D, Trespidi S, Perna F, Gatta L, Tampieri A, Ricci C, Cantelli-Forti G, Miglioli M, Biagi GL, Paolini M. The clinical role of cytochrome p450 genotypes in Helicobacter pylori management. Am J Gastroenterol. 2003 May;98(5):1010-5. doi: 10.1111/j.1572-0241.2003.07427.x.
• Background Sugimoto M, Furuta T, Shirai N, Kodaira C, Nishino M, Ikuma M, Ishizaki T, Hishida A. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Helicobacter. 2007 Aug;12(4):317-23. doi: 10.1111/j.1523-5378.2007.00508.x.
• Background Furuta T, Graham DY. Pharmacologic aspects of eradication therapy for Helicobacter pylori Infection. Gastroenterol Clin North Am. 2010 Sep;39(3):465-80. doi: 10.1016/j.gtc.2010.08.007.
• Background Scott D, Weeks D, Melchers K, Sachs G. The life and death of Helicobacter pylori. Gut. 1998 Jul;43 Suppl 1(Suppl 1):S56-60. doi: 10.1136/gut.43.2008.s56.
• Background Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet. 2005 Jun;20(3):153-67. doi: 10.2133/dmpk.20.153.
• Background Chaudhry AS, Kochhar R, Kohli KK. Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors. Indian J Med Res. 2008 Jun;127(6):521-30.
• Background Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol. 2010 Mar;69(3):222-30. doi: 10.1111/j.1365-2125.2009.03578.x.
• Background 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 Sep;8(9):1199-210. doi: 10.2217/14622416.8.9.1199.
• Background Isaza C, Henao J, Martinez JH, Sepulveda Arias JC, Beltran L. Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals. BMC Clin Pharmacol. 2007 Jul 11;7:6. doi: 10.1186/1472-6904-7-6.
• Background Arevalo-Galvis A, Trespalacios-Rangell AA, Otero W, Mercado-Reyes MM, Poutou-Pinales RA. Prevalence of cagA, vacA, babA2 and iceA genes in H. pylori strains isolated from Colombian patients with functional dyspepsia. Pol J Microbiol. 2012;61(1):33-40.
• Background Baldwin RM, Ohlsson S, Pedersen RS, Mwinyi J, Ingelman-Sundberg M, Eliasson E, Bertilsson L. Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol. 2008 May;65(5):767-74. doi: 10.1111/j.1365-2125.2008.03104.x. Epub 2008 Feb 20.
• Background Tang HL, Li Y, Hu YF, Xie HG, Zhai SD. 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. PLoS One. 2013 Apr 30;8(4):e62162. doi: 10.1371/journal.pone.0062162. Print 2013.
• Background Sugimoto M, Furuta T. Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype. World J Gastroenterol. 2014 Jun 7;20(21):6400-11. doi: 10.3748/wjg.v20.i21.6400.
• Arevalo-Galvis A, Otero-Regino WA, Ovalle-Celis GN, Rodriguez-Gomez ER, Trespalacios-Rangel AA. Prevalence of CYP2C19 polymorphism in Bogota, Colombia: The first report of allele *17. PLoS One. 2021 Jan 27;16(1):e0245401. doi: 10.1371/journal.pone.0245401. eCollection 2021.
• Arevalo Galvis A, Trespalacios Rangel AA, Otero Regino W. Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first-line triple therapy. Helicobacter. 2019 Jun;24(3):e12574. doi: 10.1111/hel.12574. Epub 2019 Mar 11.

Drugs

Indications