Genetic polymorphisms in biotransformation enzymes in Crohn's disease: association with microsomal epoxide hydrolase

Gut. 2003 Apr;52(4):547-51. doi: 10.1136/gut.52.4.547.

Abstract

Background: Mucosal biotransformation enzymes can modify toxic compounds in the gut. As chemical or oxidative stress may be involved in the aetiology of Crohn's disease, genes encoding for enzymes involved in the prevention of such stress may be candidates for genetic susceptibility to Crohn's disease.

Aim: To assess the association of Crohn's disease with genetic polymorphisms in cytochrome P450 1A1, glutathione S-transferases mu-1, pi-1, and theta-1, and epoxide hydrolase.

Methods: chi(2) square analysis was used to compare frequencies of polymorphisms between 151 patients with Crohn's disease and 149 healthy controls.

Results: In patients, a genetic polymorphism in exon 3 of the microsomal epoxide hydrolase gene was distributed significantly different compared with controls (chi(2)=23.7; p<0.0001). All other polymorphisms tested were equally distributed between patients and controls.

Conclusions: Microsomal epoxide hydrolase may play a role in the pathophysiology of Crohn's disease. Furthermore, the epoxide hydrolase gene is located on chromosome 1q, close to a region previously linked to Crohn's disease.

MeSH terms

  • Adult
  • Biotransformation / genetics
  • Chromosomes, Human, Pair 1 / genetics
  • Crohn Disease / enzymology
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • Cytochrome P-450 CYP1A1 / genetics
  • Epoxide Hydrolases / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Glutathione Transferase / genetics
  • Humans
  • Male
  • Microsomes / enzymology
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length

Substances

  • Cytochrome P-450 CYP1A1
  • Glutathione Transferase
  • Epoxide Hydrolases