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Genetic polymorphisms in biotransformation enzymes in Crohn’s disease: association with microsomal epoxide hydrolase
  1. D J de Jong,
  2. E M J van der Logt,
  3. A van Schaik,
  4. H M J Roelofs,
  5. W H M Peters,
  6. T H J Naber
  1. Department of Gastroenterology and Hepatology, University Medical Centre Nijmegen, the Netherlands
  1. Correspondence to:
    Dr D J de Jong, Department of Gastroenterology and Hepatology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands;
    d.dejong{at}gastro.azn.nl

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: χ2 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 (χ2=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.

  • Crohn’s disease
  • epoxide hydrolase
  • biotransformation enzyme
  • genetic polymorphism
  • Arg, arginine
  • CYP1A1, cytochrome P450 1A1 gene
  • EPXH, microsomal epoxide hydrolase gene
  • GSTM1, glutathione S-transferase mu-1
  • GSTP1, glutathione S- transferase pi-1
  • GSTT1, glutathione S-transferase theta-1
  • His, histidine
  • Ile, isoleucine
  • PCR, polymerase chain reaction
  • RFLP, restriction fragment length polymorphism
  • ROS, reactive oxygen species
  • Tyr, tyrosine
  • Val, valine

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