NSAID-induced antral ulcers are associated with distinct changes in mucosal gene expression.
BACKGROUND
The basis for individual variation in gastroduodenal vulnerability to NSAIDs is not well understood.


OBJECTIVE
To assess whether a gene expression signature is associated with susceptibility to gastroduodenal ulcerations.


METHODS
Twenty-five Helicobacter pylori negative adults were treated for 7 days with naproxen 500 mg b.d. Subjects underwent baseline and post-treatment endoscopy, during which biopsies were taken from antrum and duodenum. RNA extraction and cDNA synthesis were performed, followed by PCR of 23 genes relevant to mucosal injury and repair. Fold changes in gene expression were compared between subjects who developed ulcers and those who did not.


RESULTS
Compared with subjects who did not develop ulcers (n = 18), subjects who developed antral ulcers (n = 7) had significantly greater mucosal up-regulation of interleukin-8 [Fold change = 33.5 (S.E.M. = 18.5) vs. -7.7 (3.2)] and of cyclo-oxygenase-2 [2.3 (1.7) vs. -10.8 (2.2)]. Conversely, non-ulcer subjects had significantly greater up-regulation of toll-like receptor-4, cyclo-oxygenase-1 and hepatocyte growth factor [14.0 (2.2) vs. -0.8 (1.0), 9.8 (2.4) vs. 0.0 (0.7) and 8.2 (2.6) vs. -2.2 (0.3) respectively].


CONCLUSIONS
NSAID-induced antral ulcers are associated with a specific pattern of gastroduodenal mucosal gene expression. These patterns may provide an insight into the molecular basis of individual susceptibility to mucosal injury.
Desai
J C
JC
Department of Medicine (Division of Gastroenterology), The Mount Sinai Medical Center, New York, NY, USA.
Goo
T
T
Fukata
M
M
Sanyal
S
S
Dikman
A
A
Miller
K
K
Cohen
L
L
Brooks
A
A
Wang
Q
Q
Abreu
M T
MT
Aisenberg
J
J
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000494:pharmacology; D010437:Peptic Ulcer / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen