CYP2C19 genetic polymorphisms and proton pump inhibitor therapy resistance in patients with gastrooesophageal reflux disease : a preliminary observational cohort study

Abstract

Objectives: Clinical relevance of CYP2C19 genetic polymorphisms in real-world patient populations requires further investigation. This study aimed to determine the prevalence of CYP2C19 genetic variants in patients with GORD showing resistance to PPI therapy and possible clinical implications.

Methods: Patients with GORD and documented PPI resistance were identified from ambulatory reflux monitoring and endoscopy databases. EDTA blood samples were obtained for CYP2C19 genotyping using real-time polymerase chain reaction and reverse hybridisation. Genotypes (phenotypes) were categorised into: *1/*1 (normal metabolisers, NMs), *1/*17 (rapid metabolisers, RMs), *17/*17 (ultra-rapid metabolisers, UMs), *1/*2, *2/*17 (intermediate metabolisers, IMs), *2/*2 (poor metabolisers, PMs).

Results: Fifty patients were assessed (49 European ancestry, 28 male, modal age 50–59 years). Predominant resistance patterns included reflux hypersensitivity (n=19) and persistent oesophagitis (n=17). PPI therapy included esomeprazole (n=26), omeprazole (n=22), lansoprazole (n=2). Genotyping identified 26 NMs (52 %), 8 RMs (16 %), 14 IMs (28 %), 2 PMs (4 %); no UMs were identified.

Conclusions: Findings from this preliminary study indicate a higher frequency of NMs and RMs compared to IMs and PMs in this PPI-resistant cohort with GORD. Most resistance was observed to the second-generation PPI esomeprazole. A limitation was the lack of a control group comprising PPI-sensitive patients.