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

• Published in: Gut Vol. 52; no. 4; pp. 547 - 551
• Main Authors: de Jong, D J, van der Logt, E M J, van Schaik, A, Roelofs, H M J, Peters, W H M, Naber, T H J
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.04.2003; BMJ; BMJ Publishing Group LTD; Copyright 2003 by Gut
• Subjects: Adult; Age; Antioxidants; Arg; arginine; Biological and medical sciences; Biotransformation - genetics; biotransformation enzyme; Bowel disease; Chromosomes, Human, Pair 1 - genetics; Crohn Disease - enzymology; Crohn Disease - genetics; Crohn Disease - pathology; Crohns disease; Crohn’s disease; CYP1A1; Cytochrome; Cytochrome P-450 CYP1A1 - genetics; cytochrome P450 1A1 gene; Deoxyribonucleic acid; DNA; Enzymes; epoxide hydrolase; Epoxide Hydrolases - genetics; EPXH; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes; genetic polymorphism; Genetic Predisposition to Disease; Genotype & phenotype; glutathione S- transferase pi-1; glutathione S-transferase mu-1; glutathione S-transferase theta-1; Glutathione Transferase - genetics; GSTM1; GSTP1; GSTT1; His; histidine; Humans; Ile; Inflammatory Bowel Disease; isoleucine; Male; Medical sciences; Metabolism; microsomal epoxide hydrolase gene; Microsomes - enzymology; Mutation; Other diseases. Semiology; Patients; PCR; Phenotype; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; reactive oxygen species; restriction fragment length polymorphism; RFLP; ROS; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; Tyr; tyrosine; Val; valine; Human; Enzyme; Transferases; Chromosome A1; Structure gene; Genetic determinism; Epoxide hydrolase; Statistical study; Inflammatory disease; Crohn disease; Glutathione transferase; Predisposition; Ether hydrolases; Digestive diseases; Genetics; Hydrolases; Intestinal disease; Polymorphism
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.52.4.547

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.