The Relationship Between Serum Bilirubin and Crohn's Disease

Background: The oxidative stress is thought to play an important role in Crohn's disease (CD). As serum bilirubin represents the major endogenous antioxidant, this article aimed to evaluate in a clinical study, whether serum bilirubin levels and genes affecting its systemic concentrations are associated with CD. Methods: This exploratory case-control study was based on pediatric (n = 119) and adult (n = 504) patients with CD and 370 appropriate healthy control subjects. The (GT)(n) and (TA)(n) dinucleotide variations in heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) gene promoters were determined by fragment analysis. Serum bilirubin levels were compared in a subset of 90 cases and 229 controls, for whom biochemical data were available. Results: Substantially lower serum bilirubin levels were detected in patients with CD compared with controls (7.4 versus 12.1 mu mol/L, P < 10(-6)). Serum bilirubin levels were significantly lower in patients with CD within all UGT1A1*28 genotypes (P < 0.05). UGT1A1*28 homozygotes with wild-type NOD2 gene variant exhibited significant delay in CD manifestation (P = 0.004), while the protective effect of UGT1A1*28 homozygosity was lost in those patients with mutated NOD2 gene. No associations between CD risk and individual HMOX1 gene variants were observed. Conclusions: CD is associated with significantly low serum bilirubin levels, most likely as a result of increased oxidative stress accompanying this inflammatory disease. UGT1A1*28 allele homozygosity, responsible for higher bilirubin levels, seems to be an important modifier of CD manifestation.