title: NSAID-induced antral ulcers are associated with distinct changes in mucosal gene expression.
abstract: 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.
authors.affiliation: Department of Medicine (Division of Gastroenterology), The Mount Sinai Medical Center, New York, NY, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Desai
authors.forename: T
authors.initials: T
authors.lastname: Goo
authors.forename: M
authors.initials: M
authors.lastname: Fukata
authors.forename: S
authors.initials: S
authors.lastname: Sanyal
authors.forename: A
authors.initials: A
authors.lastname: Dikman
authors.forename: K
authors.initials: K
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Brooks
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: M T
authors.initials: MT
authors.lastname: Abreu
authors.forename: J
authors.initials: J
authors.lastname: Aisenberg
mesh_terms: 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*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen