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Personalizovaná terapie pacientů s gastroezofageální refluxní chorobou - metodika stanovení genového profilu CYP2C19

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Title in English Personalized therapy in patients with gastroesophageal reflux disease - methodology of CYP2C19 gene profile´s determination


Year of publication 2018
Type Article in Periodical
Magazine / Source Gastroenterologie a Hepatologie
MU Faculty or unit

Faculty of Medicine

Keywords CYP2C19*17; CYP2C19*2; Gastroesophageal reflux; Gene polymorphism; Pharmacogenetics; Poor metabolizer; Proton pump inhibitors; Ultra rapid metabolizer
Description Introduction: Conservative treatment of gastroesophageal reflux disease (GERD) is currently based on a group of drugs that effectively suppress the secretion of hydrochloric acid in the stomach, so-called proton pump inhibitors (PPI). Although these drugs do not target the cause of the disease, they are considered and accepted as the “gold standard” for the treatment of this disease. The aim of this retrospective study was to map medication of GERD patients in various phases of the disease, to analyze individual variability in the cytochrome P450 (CYP2C19) gene, and to propose an effective method for the simple determination of the gene in GERD patients. Methods: The study included 276 GERD patients with known pharmacological anamnesis who had undergone surgical treatment. The subjects included 94 patients with non-erosive reflux disease, 121 with reflux esophagitis, and 61 with Barrett’s esophagus (BE) or esophageal adenocarcinoma (EAC). Genotypes of two polymorphisms in the CYP2C19 gene (*17 rs12248560 and *2 rs4244285) were determined using quantitative polymerase chain reaction. Results: More than 90% patients were treated with PPI (omeprazole/lansoprazole/pantoprazole). Although the prescribed PPI dosing in the studied cohort was consistent with recommendations for maintenance therapy, the patients’ ability to metabolize the active substance was not considered. Carriers of genotype combinations containing the CYP2C9*17 variant, which determines the ultra-rapid metabolizer (UM) phenotype, were less likely to co-occur with the CYP2C19*2 variant, which determines the intermediate or “poor“ metabolizer (IM or PM) phenotype, than individuals with the standard functioning CYP2C19 enzyme (p = 0.001). The frequencies of combinations of genotypes (haplogenotypes) and resulting UM/IM/PM phenotypes were 37.3/16.7/1.4% in GERD patients. Conclusion: Prior to initiating PPI pharmacotherapy in GERD patients, determination of CYP2C19 haplogenotypes (CYP2C19*17 and *2 variants) should be performed due to frequent occurence of these variants in population and their functional metabolic significance. We presume that this approach will increase the effectiveness of pharmacotherapy, improve patient quality of life, and very likely help prevent/reduce the risk of the development of more serious conditions, such as BE and EAC. The non-standard ability to metabolize PPI in GERD patients may be one of the indicators for surgical intervention.
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