Genetic polymorphisms of CYP2D6 oxidation in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) consists of ulcerative colitis and Crohn's disease, both of which are associated with increased colorectal cancer risk. The relationship between genetically determined polymorphic metabolism of exogenous substances by oxidation catalyzed by CYP2D6 isoenzyme and susceptibility to cancer has aroused great interest. We determined whether there was an association between susceptibility to inflammatory bowel disease and particularly to CYP2D6 genotypes. The study was carried out in 39 patients with IBD. The control group consisted of 129 healthy volunteers. The CYP2D6 genotypes were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method with DNA extracted from peripheral blood. Among 39 patients with inflammatory bowel disease, extensive metabolizer (EM) genotype constituted 97.4%. One patient (2.6%) was poor metabolizer with CYP2D6*4/CYP2D6*4 genotype. Results obtained in the inflammatory bowel disease group did not differ significantly from those of the control group. Although the odds ratio for EM metabolizers was about 3.8-fold greater in the group of patients with inflammatory bowel disease, this association was not statistically significant. This data also showed no overall statistically significant association between alleles and incidence risk of inflammatory bowel disease [odds ratio (OR) of 1.36 for CYP2D6*1 allele, 0.83 for CYP2D6*3 allele, and 0.74 for CYP2D6*4 allele]. The present results suggest that EM genotype may be the risk factor of inflammatory bowel disease. Future studies are needed to confirm our assumptions on larger group of patients.