Common polymorphisms in the microsomal epoxide hydrolase and N-acetyltransferase 2 genes in association with inflammatory bowel disease in the Danish population.

ABSTRACT

INTRODUCTION: Chronic inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the intestinal mucosa. Reactive molecules play a central role in altering the intestinal permeability, which may induce or sustain an immune response. Changes in detoxification of substances that causes epithelial damage may confer susceptibility to IBD. Hence, polymorphic enzymes involved in the detoxification processes may be risk factors of IBD. METHODS: The two biotransformation enzymes microsomal epoxide hydrolase and N-acetyltransferase 2 were genotyped using TaqMan based real-time PCR in 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls. RESULTS: No association was found between the genotypes of low microsomal epoxide hydrolase activity or slow N-acetyltransferase 2 acetylator status and IBD. An association was found between microsomal epoxide hydrolase and less than 40 years of age at diagnosis of Crohn's disease and microsomal epoxide hydrolase and azathiporine use in patients with ulcerative colitis. No other evident phenotypic associations were found for the two enzymes and either ulcerative colitis or Crohn's disease. A possible modification of smoking on microsomal epoxide hydrolase genotypes was found. CONCLUSION: Microsomal epoxide hydrolase and N-acetyltransferase 2 genotypes appear not to be individual risk factors of IBD, or to be important in relation to phenotypic characteristics of IBD.