Abstract
BackgroundCyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1α/β, interferon-γ and tumor necrosis factor-α produced by inflammatory cells.AimThe aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms −1195 A→G and −765G→C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population.MethodsGenomic DNA of 525 patients with Crohn's disease (CD), 211 patients with ulcerative colitis (UC) and 973 healthy controls was genotyped for the −1195 A→G (rs689466) and −765G→C (rs20417) polymorphisms. Distribution of genotypes in patients and controls were compared and genotype-phenotype interactions were investigated.ResultsThe genotype distribution of the −1195A→G polymorphism was not different between the patients with CD or UC and the control group. The −765GG genotype was more prevalent in CD patients compared to controls with an OR of 1.33 (95%CI 1.04–1.69, p<0.05). The −765GC and −765CC genotype carriers showed a tendency to be less frequent in patients with CD compared to controls, with ORs of 0.78 (95%CI: 0.61–1.00) and 0.49 (95%CI 0.22–1.08), respectively. Combining homozygous and heterozygous patients with the −765C allele showed a reduced risk for developing CD, with an OR of 0.75 (95%CI: 0.59–0.96). In the context of this, the G−1195G−765/A−1195C−765 diplotype was significantly less common in patients with CD compared to controls, with an OR of 0.62 (95%CI: 0.39–0.98). For UC however, such an effect was not observed. No correlation was found between COX-2 diplotypes and clinical characteristics of IBD.ConclusionsThe −765G→C polymorphism was associated with a reduced risk for developing Crohn's disease in a Dutch population.
Highlights
Inflammatory bowel disease (IBD) is an idiopathic, chronic, relapsing auto inflammatory disorder of the gastro-intestinal tract
Phenotypes of the patients were described according to age of onset, necessity of surgery, family history of IBD, the occurrence of extra-intestinal manifestations and maximum extent of disease according to the Vienna [19] and Montreal [20] classifications for Crohn’s disease and ulcerative colitis respectively
We investigated in patients with IBD whether the 21195ARG and 2765GRC polymorphisms were associated with development of mucosal dysplasia or colon cancer
Summary
Inflammatory bowel disease (IBD) is an idiopathic, chronic, relapsing auto inflammatory disorder of the gastro-intestinal tract. A dysregulated immune response against the intestinal microbiota in genetic susceptible individuals has been heavily implicated in the pathogenesis of inflammatory bowel disease [2]. Genes involved in inflammatory responses are under investigation to look for variants predisposing to IBD. Cyclooxygenase (COX) is a modifier gene and key enzyme in the conversion of free arachidonic acid into prostaglandins and is involved in the regulation of inflammatory processes through its products, mainly prostaglandin E2 (PGE2) [3]. Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1a/b, interferon-c and tumor necrosis factor-a produced by inflammatory cells
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