Evaluation of CYP2C19 Gene Polymorphisms in Patients with Acid Peptic Disorders Treated with Esomeprazole

Abstract

Background CYP2C19 is a highly polymorphic gene that encodes an enzyme with the same name and whose function is associated with the metabolism of many important drugs, such as proton pump inhibitors (such as esomeprazole, which is used for the treatment of acid peptic disease). Genetic variants in CYP2C19 alter protein function and affect drug metabolism. This study aims to genotypically and phenotypically characterize the genetic variants in the CYP2C19 gene in 12 patients with acid peptic disorders and different therapeutic profiles to proton pump inhibitor (PPI) drugs. The patients were randomly selected from a controlled, randomized and blinded clinical pilot trial of 33 patients. We determined the presence and frequency of single nucleotide polymorphisms (SNPs) within exons 1–5 and 9, the intron-exon junctions, and a fragment in the 3ʹ UTR region of the CYP2C19 gene using Sanger sequencing. Undescribed polymorphisms were analyzed by free online bioinformatics tools to evaluate the potential molecular effects of these genetic variants. Results We identified nine polymorphisms, six of which had no reported functions. One of these genetic variants, with a functional impact, not yet reported (p.Arg132Trp) was predicted by bioinformatic tools as potentially pathogenic. This finding suggests that p.Arg132Trp could be related to poor metabolizers of drugs metabolized by CYP2C19. Conclusion We identified the genotype spectrum of variants in CYP2C19 . The genotype spectrum of variants in CYP2C19 could predict the treatment response and could support to evaluate clinical efficacy in patients treated with esomeprazole.

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease

“… 19 In a small study involving 12 patients, it was observed that after a 14-day course of esomeprazole treatment, the duration of pH > 4 recorded in 24-hour monitoring did not differ significantly across different phenotypes. 4 Conversely, another study demonstrated that CYP2C19 UMs displayed a statistically significant increase in duration during which the pH remained below 4. 20 For future studies, it would be interesting to compare DeMeester scores among different metabolizer groups while on PPI therapy using a larger patient population.…”

“… 3 Still, some variance exists among different PPIs: first-generation PPIs, including omeprazole and pantoprazole are mainly metabolized by CYP2C19 with secondary involvement of CYP3A4, while lansoprazole is primarily metabolized by both. 4–6 Second-generation PPIs, including rabeprazole and esomeprazole, are less dependent on CYP2C19 pathway. 5 , 6 Dexlansoprazole, another second-generation PPI, shares a similar metabolic pathway to lansoprazole.…”

Association Study of Esomeprazole Pharmacokinetics and CYP2C19 Gene Polymorphisms

“…An abundance of scientific investigations 11,12 have compellingly illustrated that gene polymorphism exerts a substantial influence on the activity of metabolic enzymes. This leads to discrepancies in enzyme expression and function among individuals possessing different genotypes, thereby potentially instigating variations in drug absorption, distribution, and metabolism.…”