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

Abstract

Lorena Díaz-Ordóñez,1– 3 Diana Ramírez-Montaño,1– 3 Estephania Candelo,2– 4 Carolina González-Restrepo,1 Sebastián Silva-Peña,1 Carlos Arturo Rojas,5 Mario Sepulveda Copete,5 Hector Raul Echavarria,6 Harry Pachajoa1– 3 1Basic Medical Science Department, Faculty of Health Sciences, Universidad Icesi, Cali, Colombia; 2Clinical Genetic Department, Fundación Valle del Lili, Cali, Colombia; 3Research Centre in Rare Diseases and Congenital Abnormalities (CIACER), Universidad Icesi, Cali, Colombia; 4Research Centre, Fundación Valle de Lili, Cali, Colombia; 5Gastroenterology Department, Fundacion Valle del Lili, Cali, Colombia; 6Centro Medico Imbanaco, Cali, ColombiaCorrespondence: Estephania Candelo Calle 18 122-135, Cali, 76003, ColombiaTel [phone]Fax + 57 2 555 1441Email [email protected]: 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.Keywords: single nucleotide polymorphism, cytochrome P450 CYP2C19, pharmacogenetics, computational biology, treatment failure, proton pump inhibitors

Keywords

• single nucleotide polymorphism
• cytochrome p450 cyp2c19
• pharmacogenetics
• computational biology
• treatment failure
• proton pump inhibitors