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

Azucena Arévalo-Galvis, William A Otero-Regino, Gloria N Ovalle-Celis, Eliana R Rodríguez-Gómez, Alba A Trespalacios-Rangel, Azucena Arévalo-Galvis, William A Otero-Regino, Gloria N Ovalle-Celis, Eliana R Rodríguez-Gómez, Alba A Trespalacios-Rangel

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Prevalence of polymorphisms of CYP2C19.
Fig 1. Prevalence of polymorphisms of CYP2C19.
The distribution of CYP2C19 polymorphisms in Bogotá, Colombia. The high prevalence of polymorphisms compatible with extensive and ultrarapid metabolizers of PPIs is evident. EM: extensive metabolizer, UM: ultrarapid metabolizer, IM: intermediate metabolizer, PM: poor metabolizer.
Fig 2. CYP2C19*17 sequence.
Fig 2. CYP2C19*17 sequence.
An example of a CYP2C19*17 sequence analysis. For this purpose, the sequence was compared with two wild-type reference sequences (GenBank Access: AL583836 and NG_008384.3.18). The sequence analysis shows the SNP at position -806(C >T) (quadrate) relative to translation start that is surrounded by the sequence GTATCT (blue underline).

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