title: A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated with a decreased risk for Crohn's disease.
abstract: BACKGROUND
  An imbalance between the production of reactive oxygen species (ROS) and their capturing by antioxidants results in oxidative stress, this may play an important role in the pathogenesis of inflammatory bowel disease (IBD). Since bilirubin is an important endogenous antioxidant, increased levels of bilirubin may protect against IBD. UDP-glucuronosyltransferase 1A1 (UGT1A1) is the only enzyme involved in the conjugation of bilirubin and the common UGT1A1*28 allele in the UGT1A1 gene, which is strongly associated with Gilbert's syndrome in Caucasians, results in elevated plasma bilirubin levels.
  
  
  OBJECTIVE
  To test the hypothesis that the UGT1A1*28 allele is associated with lower disease susceptibility to, and disease behavior within, IBD. In addition, a possible altered risk for developing IBD-drug related side-effects was explored.
  
  
  METHODS
  Genomic DNA of 751 patients with IBD (209 patients with ulcerative colitis and 542 patients with Crohn's disease) and 930 healthy controls was genotyped for the UGT1A1*28 promoter polymorphism, and genotype distribution was compared between patients and controls. Genotype phenotype interactions were also investigated.
  
  
  RESULTS
  Patients with Crohn's disease significantly less often bear the UGT1A1*28 homozygous genotype compared to the control group, with an odds ratio of 0.64, 95% CI: 0.42-0.98. The ulcerative colitis group showed no significant differences compared to controls.
  
  
  CONCLUSIONS
  The homozygous state of the UGT1A1*28 polymorphism, associated with higher serum bilirubin levels, may be protective for the development of Crohn's disease, suggesting that the anti-oxidant capacity of bilirubin may play a part.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. h.devries@mdl.umcn.nl
authors.forename: Hilbert S
authors.initials: HS
authors.lastname: de Vries
authors.forename: Rene H M
authors.initials: RH
authors.lastname: Te Morsche
authors.forename: Kevin
authors.initials: K
authors.lastname: Jenniskens
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: de Jong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000097:blood / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D015415:Biomarkers; D004247:DNA; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme