Prevalence of CYP2C19 polymorphism in Bogotá, Colombia: The first report of allele *17

PLoS One. 2021 Jan 27;16(1):e0245401. doi: 10.1371/journal.pone.0245401. eCollection 2021.

Abstract

Introduction: 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 Helicobacter pylori (H. pylori) 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.

Objective: To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogotá, Colombia.

Methods: This observational study was conducted in Bogotá between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia, H. pylori infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche®), and PCR-RFLP was used to determine the presence of polymorphism *17.

Results: The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Colombia
  • Cytochrome P-450 CYP2C19 / genetics*
  • Dyspepsia / drug therapy
  • Dyspepsia / genetics
  • Female
  • Gastroesophageal Reflux / drug therapy
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Proton Pump Inhibitors / pharmacology
  • Proton Pump Inhibitors / therapeutic use
  • Stomach Ulcer / drug therapy
  • Stomach Ulcer / genetics

Substances

  • Proton Pump Inhibitors
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19

Associated data

  • ClinicalTrials.gov/NCT03650543

Grants and funding

The project is funded by the Vice-rectory for research Pontificia Universidad Javeriana (Bogotá, Colombia), grant No. 00004554, “Effect of CYP2C19 polymorphism on Helicobacter pylori eradication”. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.