Gene expression of gastric mucosa during therapeutic acid inhibition

The effect on mucosal gene expression of potent acid inhibition with proton pump inhibitors (PPI’s) given to humans in ordinary, therapeutic doses is virtually unknown. Eight patients suffering from gastro-oesophageal reflux disease were included in this study. Endoscopic biopsies were taken from the corpus mucosa before and towards the end of a three-month treatment with the PPI esomeprazole 40 mg daily. Total RNA was extracted and samples (2 microgram total RNA) were labeled for microarray analysis. For each patient, RNA from both time points were labeled and hybridized to a single array. The gene expression patterns for 7700 genes were analyzed and differentially expressed genes were identified using one-sample Student t test. The aim of this study was, by use of cDNA microarray, to get an overview of the gene expression pattern in gastric corpus mucosa in patients after three months’ treatment with the proton pump inhibitor esomeprazole. Further characterization of the functional roles of genes whose expression is modulated by potent acid inhibition may give new insight into the molecular responses to this therapeutic intervention, including the mucosal response to the moderately increased gastrin levels encountered in clinical practice. Keywords: Repeat sample group, treatment analysis The series is composed of 8 hybridizations for analysis of differentially expressed genes in the gastric mucosa of patients treated with 40 mg omeprazole (Losec, Astra AB, Gothenburg, Sweden) once daily for 90 days. Biopsy speciments were taken form the oxyntic mucosa before treatment and during the last week of treatment. Total RNA from patients before treatment (2 microgram each) and patients after treatment (2 microgram each) were reverse transcribed and labeled with Cy3- and Cy5-attached dendrimer, respectively, mixed and hybridized using 3DNA Array Detection Submicro kit as described in the manufacturer's protocols (Genisphere, Montvale, NJ). The labeling reactions were also spiked with exogenous control RNAs (Stratagene). No technical replicates or dye-swabs were included.