title: The relationship between serum bilirubin and Crohn's disease.
abstract: 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). 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.
authors.affiliation: *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.
authors.forename: Martin
authors.initials: M
authors.lastname: Leníček
authors.forename: Dana
authors.initials: D
authors.lastname: Duricová
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hradsky
authors.forename: Petra
authors.initials: P
authors.lastname: Dušátková
authors.forename: Alena
authors.initials: A
authors.lastname: Jirásková
authors.forename: Milan
authors.initials: M
authors.lastname: Lukáš
authors.forename: Petr
authors.initials: P
authors.lastname: Nachtigal
authors.forename: Libor
authors.initials: L
authors.lastname: Vítek
mesh_terms: D000293:Adolescent; D000328:Adult; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D015415:Biomarkers; D014453:Glucuronosyltransferase; D051547:Heme Oxygenase-1; D000099148:UGT1A1 Enzyme