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Changes in gene expression of gastric mucosa during therapeutic acid inhibition

Nørsett, Kristin G.a; Lægreid, Astrida; Kusnierczyk, Waclawc; Langaas, Metted; Ylving, Sonjaa; Fossmark, Reidara e; Myhre, Simena; Falkmer, Stureb f; Waldum, Helge L.a e; Sandvik, Arne K.a e

European Journal of Gastroenterology & Hepatology: July 2008 - Volume 20 - Issue 7 - p 613-623
doi: 10.1097/MEG.0b013e3282f5dc19
Original Articles: Oesophageal and Gastric Disorders
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Background Long-term therapy with potent acid inhibitors is a common treatment for gastro-esophageal reflux disease. Administration of proton pump inhibitors (PPIs) causes profound and continuous hypochlorhydria by inhibition of the proton pump in gastric parietal cells. Long-term hypergastrinaemia increases mucosal thickness and enterochromaffin-like cell density in oxyntic mucosa.

Objective The aim of this study was to see whether this very common clinical intervention induces significant changes in the gastric mucosal gene expression pattern.

Methods Seven patients suffering from gastro-esophageal reflux disease were included in this study. Endoscopic biopsies were taken from the corpus mucosa before and toward the end of a 3-month treatment with the PPI esomeprazole.

Results Microarray analysis identified 186 differentially expressed genes. A high proportion of genes with changed gene expression levels during PPI treatment are involved in proliferation, apoptosis, and stress response.

Conclusion This study identified many genes that were not previously known to be affected by inhibition of gastric acid secretion. Further characterization of the functional roles of genes whose expression is modulated by potent acid inhibition may give new insight into the biological responses to potent acid inhibition, including the mucosal response to the moderately increased gastrin levels encountered in clinical practice.

Departments of aCancer Research and Molecular Medicine

bLaboratory Medicine, Children's and Women's Health, Faculty of Medicine

Departments of cComputer and Information Science

dMathematical Sciences, Faculty of Information Technology, Mathematics, and Electrical Engineering, Norwegian University of Science and Technology

eSection of Gastroenterology, St Olav's University Hospital, Trondheim, Norway

fLaboratory of Clinical Pathology and Cytology, County Hospital Ryhov, Sweden

Correspondence to Kristin G. Nørsett, PhD, Department of Cancer Research and Molecular Medicine, NTNU, Trondheim N-7489, Norway

Tel: +47 73598802; fax: +47 73598613;

e-mail: kristin.norsett@ntnu.no

Received 20 August 2007 Accepted 15 December 2007

© 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins