NSAID-induced antral ulcers are associated with distinct changes in mucosal gene expression

The basis for individual variation in gastroduodenal vulnerability to NSAIDs is not well understood.

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

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.

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].

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.