Changes in gene expression of gastric mucosa during therapeutic acid inhibition.
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.


CONCLUSIONS
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.
Nørsett
Kristin G
KG
Department of Cancer Research and Molecular Medicine, NTNU, Norway. kristin.norsett@ntnu.no
Laegreid
Astrid
A
Kusnierczyk
Waclaw
W
Langaas
Mette
M
Ylving
Sonja
S
Fossmark
Reidar
R
Myhre
Simen
S
Falkmer
Sture
S
Waldum
Helge L
HL
Sandvik
Arne K
AK
D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D064098:Esomeprazole / Q000494:pharmacology / Q000627:therapeutic use; D004945:Esophagoscopy; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005755:Gastrins / Q000097:blood; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D005755:Gastrins; D054328:Proton Pump Inhibitors; D064098:Esomeprazole