The functional -765G→C polymorphism of the COX-2 gene may reduce the risk of developing crohn's disease.
BACKGROUND
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-1α/β, interferon-γ and tumor necrosis factor-α produced by inflammatory cells.


OBJECTIVE
The 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.


METHODS
Genomic 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.


RESULTS
The 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(-1195)G(-765)/A(-1195)C(-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.


CONCLUSIONS
The -765G→C polymorphism was associated with a reduced risk for developing Crohn's disease in a Dutch population.
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. h.devries@mdl.umcn.nl
Hilbert S
HS
de Vries
Rene H M
RH
te Morsche
Martijn G H
MG
van Oijen
Iris D
ID
Nagtegaal
Wilbert H M
WH
Peters
Dirk J
DJ
de Jong
D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human