{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:55:44Z","timestamp":1765486544448,"version":"3.40.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana","doi-asserted-by":"crossref","award":["00004554"],"award-info":[{"award-number":["00004554"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Introduction<\/jats:title><jats:p>Proton pump inhibitors (PPIs) are a group of drugs that are essential for the treatment of acid-related disorders, such as gastroesophageal reflux (GERD), dyspepsia, gastric ulcers and<jats:italic>Helicobacter pylori<\/jats:italic>(<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>) infection. PPIs such as omeprazole, esomeprazole, pantoprazole and lansoprazole are metabolized by the CYP2C19 enzyme, which is encoded by a polymorphic gene. Four polymorphisms have an impact on the speed of PPI metabolism: CYP2C19*1\/*1 (extensive metabolizers), CYP2C19*2\/*2 (intermediate metabolizers), CYP2C19*3\/*3 (poor metabolizers) and CYP2C19*17\/*17 (ultrarapid metabolizers). Extensive and ultrarapid metabolizers inactivate PPIs quickly, which consequently causes low plasma concentrations of PPIs, while intermediate or poor metabolizers have higher plasma concentrations of PPIs and, therefore, PPIs have greater therapeutic efficacy in individuals with these polymorphisms.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Objective<\/jats:title><jats:p>To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogot\u00e1, Colombia.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Methods<\/jats:title><jats:p>This observational study was conducted in Bogot\u00e1 between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia,<jats:italic>H<\/jats:italic>.<jats:italic>pylori<\/jats:italic>infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche<jats:sup>\u00ae<\/jats:sup>), and PCR-RFLP was used to determine the presence of polymorphism *17.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Results<\/jats:title><jats:p>The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%).<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Conclusion<\/jats:title><jats:p>The population studied consisted mainly of extensive and ultrarapid PPI metabolizers. These findings show that it is necessary to increase PPI doses in this group of subjects or to use PPIs that are not metabolized by CYP2C19 (rabeprazole). This is the first Colombian work to identify ultrarapid metabolizers.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0245401","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T18:26:17Z","timestamp":1611771977000},"page":"e0245401","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prevalence of CYP2C19 polymorphism in Bogot\u00e1, Colombia: The first report of allele *17"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0193-5089","authenticated-orcid":true,"given":"Azucena","family":"Ar\u00e9valo-Galvis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6825-9014","authenticated-orcid":true,"given":"William A.","family":"Otero-Regino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria N.","family":"Ovalle-Celis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5511-9402","authenticated-orcid":true,"given":"Eliana R.","family":"Rodr\u00edguez-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba A.","family":"Trespalacios-Rangel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"issue":"2","key":"pone.0245401.ref001","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nrd1010","article-title":"A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole","volume":"2","author":"L Olbe","year":"2003","journal-title":"Nat Rev Drug Discov"},{"issue":"Suppl 2","key":"pone.0245401.ref002","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2036.2006.02943.x","article-title":"Review article: the clinical pharmacology of proton pump inhibitors","volume":"23","author":"G Sachs","year":"2006","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0245401.ref003","first-page":"CD011194","article-title":"Proton Pump inhibitor for functional dyspepsia","volume":"3","author":"MI Pinto-S\u00e1nchez","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0245401.ref004","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ajg.2012.444","article-title":"Guidelines for the diagnosis and management of gastroesophageal reflux disease","volume":"108","author":"PO Katz","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"pone.0245401.ref005","first-page":"79","article-title":"Optimal therapy for Helicobacter pylori infections","volume":"8","author":"E Rimbara","year":"2011","journal-title":"Rev. Gastroenterol. Hepatol"},{"key":"pone.0245401.ref006","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/s11894-008-0098-4","article-title":"Pharmacology of proton pump inhibitors","volume":"10","author":"JM Shin","year":"2008","journal-title":"Curr Gastroenterol Rep"},{"issue":"1","key":"pone.0245401.ref007","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2174\/1389450118666170125144557","article-title":"Cytochrome P450 Structure, Function and Clinical Significance: A Review","volume":"19","author":"P Manikandan","year":"2018","journal-title":"Curr Drug Targets"},{"issue":"1","key":"pone.0245401.ref008","first-page":"78","article-title":"Cytochrome P450 proteins: retention and distribution from the endoplasmic reticulum","volume":"13","author":"EP Neve","year":"2010","journal-title":"Curr Opin Drug Discov Devel"},{"issue":"5","key":"pone.0245401.ref009","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1211\/jpp.61.05.0002","article-title":"Dressman JB Cytochrome P450-mediated metabolism in the human gut wall","volume":"61","author":"K Thelen","year":"2009","journal-title":"J Pharm Pharmacol"},{"issue":"3","key":"pone.0245401.ref010","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1365-2125.2009.03578.x","article-title":"Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17","volume":"69","author":"A Li-Wan-Po","year":"2010","journal-title":"Br J Clin Pharmacol"},{"issue":"4","key":"pone.0245401.ref011","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/17425255.2018.1461835","article-title":"Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine","volume":"14","author":"N El Rouby","year":"2018","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"pone.0245401.ref012","first-page":"966","article-title":"Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes","volume":"28","author":"A Abel\u00f6","year":"2000","journal-title":"Drug Metab Dispos"},{"issue":"Suppl 6","key":"pone.0245401.ref013","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1365-2036.2004.02161.x","article-title":"Review article: relationship between the metabolism and efficacy of proton pump inhibitors\u2013focus on rabeprazole","volume":"20","author":"J Horn","year":"2004","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0245401.ref014","first-page":"521","article-title":"Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors","volume":"127","author":"AS Chaudhry","year":"2008","journal-title":"Indian J Med Res"},{"issue":"1","key":"pone.0245401.ref015","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jcph.977","article-title":"Association Between CYP2C19*17 Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal Reflux","volume":"58","author":"JP Franciosi","year":"2018","journal-title":"J Clin Pharmacol"},{"issue":"4","key":"pone.0245401.ref016","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/jgh.13233","article-title":"Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis","volume":"31","author":"H Ichikawa","year":"2016","journal-title":"J Gastroenterol Hepatol"},{"issue":"9","key":"pone.0245401.ref017","first-page":"1","article-title":"A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease","volume":"30","author":"L Hillman","year":"2017","journal-title":"Dis Esophagus"},{"issue":"11","key":"pone.0245401.ref018","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.3748\/wjg.v23.i11.2060","article-title":"Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy","volume":"23","author":"F Kawara","year":"2017","journal-title":"World J Gastroenterol"},{"issue":"4","key":"pone.0245401.ref019","doi-asserted-by":"crossref","first-page":"337","DOI":"10.22516\/25007440.108","article-title":"Prevalencia de s\u00edntomas del reflujo gastroesof\u00e1gico y factores asociados: una encuesta poblacional en las principales ciudades de Colombia","volume":"31","author":"DB P\u00e1ramo","year":"2016","journal-title":"Rev Col Gastroenterol"},{"issue":"2","key":"pone.0245401.ref020","first-page":"267","article-title":"Richter and Joel H. Rubenstein","volume":"154","author":"E Joel","year":"2018","journal-title":"Presentation and Epidemiology of Gastroesophageal Reflux Disease Gastroenterology"},{"issue":"2","key":"pone.0245401.ref021","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/apt.12355","article-title":"Talley Functional dyspepsia: the economic impact to patients","volume":"38","author":"B. E.","year":"2013","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0245401.ref022","doi-asserted-by":"crossref","first-page":"e12574","DOI":"10.1111\/hel.12574","article-title":"Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first\u2010line triple therapy","volume":"24","author":"A Ar\u00e9valo","year":"2019","journal-title":"Helicobacter"},{"issue":"2","key":"pone.0245401.ref023","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1053\/j.gastro.2017.04.022","article-title":"Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis","volume":"153","author":"JKY Hooi","year":"2017","journal-title":"Gastroenterology"},{"issue":"3","key":"pone.0245401.ref024","first-page":"14","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"81","author":"General Assembly of the World Medical Association","year":"2014","journal-title":"J Am Coll Dent"},{"issue":"2","key":"pone.0245401.ref025","first-page":"274","article-title":"What everybody should know about good clinical practices","volume":"35","author":"L Osorio","year":"2015","journal-title":"Biomedica"},{"key":"pone.0245401.ref026","doi-asserted-by":"crossref","first-page":"279","DOI":"10.5946\/ce.2015.48.4.279","article-title":"Introduction to Starting Upper Gastrointestinal Endoscopy: Proper Insertion, Complete Observation, and Appropriate Photographing","volume":"48","author":"KS Park","year":"2015","journal-title":"Clin Endosc"},{"issue":"6","key":"pone.0245401.ref027","first-page":"743","article-title":"Update on endoscopic tissue sampling devices","volume":"63","author":"A Barkum","year":"2010","journal-title":"Gastrintest Endos"},{"key":"pone.0245401.ref028","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1053\/j.gastro.2015.07.040","article-title":"American Gastroenterological Association Institute Technical Review on the Role of Upper Gastrointestinal Biopsy to Evaluate Dyspepsia in the Adult Patient in the Absence of Visible Mucosal Lesions","volume":"149","author":"I. John","year":"2015","journal-title":"Gastroenterology"},{"issue":"5","key":"pone.0245401.ref029","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/j.1365-2125.2008.03104.x","article-title":"Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers","volume":"65","author":"RM Baldwin","year":"2008","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"pone.0245401.ref030","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.clpt.2005.10.002","article-title":"A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants","volume":"79","author":"SC Sim","year":"2006","journal-title":"Clin Pharmacol Ther"},{"key":"pone.0245401.ref031","first-page":"6","article-title":"Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals","volume":"7","author":"C Isaza","year":"2007","journal-title":"BMC Clin Gastroenterol"},{"key":"pone.0245401.ref032","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1046\/j.1365-2125.1998.t01-1-00702.x","article-title":"Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole","volume":"45","author":"T Andersson","year":"1998","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"pone.0245401.ref033","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10620-018-4927-5","article-title":"Refractory Heartburn: A Fass OZ Challenging Problem in Clinical Practice","volume":"63","author":"G Domingues","year":"2018","journal-title":"Dig Dis Sci"},{"key":"pone.0245401.ref034","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1053\/j.gastro.2017.07.049","article-title":"Management of Gastroesophageal Reflux Disease","volume":"154","author":"CP Gyawali","year":"2018","journal-title":"Gastroenterology"},{"issue":"1","key":"pone.0245401.ref035","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11938-019-00224-7","article-title":"Overlap Between GERD and Functional Esophageal Disorders-a Pivotal Mechanism for Treatment Failure","volume":"17","author":"OZ Fass","year":"2019","journal-title":"Curr Treat Options Gastroenterol"},{"key":"pone.0245401.ref036","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1053\/j.gastro.2016.02.012","article-title":"Functional Esophageal Disorders","volume":"150","author":"Q Aziz","year":"2016","journal-title":"Gastroenterology"},{"issue":"10","key":"pone.0245401.ref037","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1111\/apt.13588","article-title":"Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype","volume":"43","author":"T Kagami","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0245401.ref038","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2165\/11530810-000000000-00000","article-title":"Patient satisfaction with switching to esomeprazole from existing proton pump inhibitor therapy for gastro-oesophageal reflux disease: an observational, multicentre study","volume":"29","author":"R J Hoogendoorn","year":"2009","journal-title":"Clin Drug Investig"},{"key":"pone.0245401.ref039","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1038\/ajg.2010.368","article-title":"The gain in quality-adjusted life months by switching to esomeprazole in those with continued reflux symptoms in primary care: EncomPASS\u2013a cluster-randomized trial","volume":"105","author":"P Moayyedi","year":"2010","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"pone.0245401.ref040","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1159\/000497775","article-title":"Efficacy of Vonoprazan, a Novel Potassium-Competitive Acid Blocker, in Patients with Proton Pump Inhibitor-Refractory Acid Reflux","volume":"101","author":"J Akiyama","year":"2020","journal-title":"Digestion"},{"issue":"4","key":"pone.0245401.ref041","doi-asserted-by":"crossref","first-page":"e62162","DOI":"10.1371\/journal.pone.0062162","article-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","volume":"8","author":"HL Tang","year":"2013","journal-title":"PLOS ONE"},{"key":"pone.0245401.ref042","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1007\/s10620-014-3093-7","article-title":"Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance","volume":"59","author":"JY Lee","year":"2014","journal-title":"Dig Dis Sci"},{"issue":"6","key":"pone.0245401.ref043","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1523-5378.2008.00643.x","article-title":"Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis","volume":"13","author":"F Zhao","year":"2008","journal-title":"Helicobacter"},{"issue":"3","key":"pone.0245401.ref044","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.gtc.2010.08.007","article-title":"Pharmacologic aspects of eradication therapy for Helicobacter pylori Infection","volume":"39","author":"T Furuta","year":"2010","journal-title":"Gastroenterol Clin North Am"},{"key":"pone.0245401.ref045","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.mgene.2016.06.004","article-title":"Rapid and ultra-rapid metabolizers with CYP2C19*17 polymorphism do not respond to standard therapy with proton pump inhibitors","volume":"9","author":"N Deshpande","year":"2016","journal-title":"Meta Gene"},{"key":"pone.0245401.ref046","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.gtc.2015.05.004","article-title":"Practical Aspects in Choosing a Helicobacter pylori Therapy","volume":"44","author":"J Molina","year":"2015","journal-title":"Gastroenterol Clin N Am"},{"key":"pone.0245401.ref047","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1053\/bega.2001.0188","article-title":"Current role of acid suppressants in Helicobacter pylori eradication therapy","volume":"15","author":"J Labenz","year":"2001","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"pone.0245401.ref048","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/j.1365-2036.2008.03807.x","article-title":"Meta-analysis: high-dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication","volume":"28","author":"A Villoria","year":"2008","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0245401.ref049","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1046\/j.1365-2036.2002.01270.x","article-title":"Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis","volume":"16","author":"M Vallve","year":"2002","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0245401.ref050","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/clpt.2012.96","article-title":"Pharmacogenomics knowledge for personalized medicine","volume":"92","author":"M Whirl-Carrillo","year":"2012","journal-title":"Clin Pharmacol Ther"},{"issue":"4","key":"pone.0245401.ref051","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1053\/j.gastro.2018.07.009","article-title":"Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference","volume":"155","author":"ES Dellon","year":"2018","journal-title":"Gastroenterology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T10:11:11Z","timestamp":1697710271000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245401"}},"subtitle":[],"editor":[{"given":"Jed N.","family":"Lampe","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,27]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0245401","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,1,27]]}}}