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 μmol/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.
Article first published online 8 January 2014
*Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;
†IBD Clinical and Research Center, ISCARE I.V.F. Lighthouse, Prague, Czech Republic;
‡Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;
§Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Prague, Czech Republic; and
‖4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Reprints: Libor Vítek, MD, PhD, 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, U Nemocnice 2, Praha 2, 128 08 Prague, Czech Republic (e-mail: email@example.com).
Supported by Grants SVV 266516/2013 and PRVOUK 4102280002 from the Czech Ministry of Education, and RVO VFN64165 from the Czech Ministry of Health.
The authors have no conflicts of interest to disclose.
Received November 12, 2013
Accepted November 21, 2013