title: Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation.
abstract: BACKGROUND
  Oxidative stress is a major mediator of adverse outcome after kidney transplantation. Bilirubin is produced by heme oxygenase-1 (HO-1), catalyzed by UDP-glucuronosyltransferase (UGT1A1), and has potential as an antioxidant. In this study, we investigated the effects of HO-1 and UGT1A1 sequence variations on kidney allograft outcomes.
  
  
  METHODS
  Clinical data were collected from 429 Korean recipients who underwent kidney transplantation from 1990-2008. Genotyping for UGT1A1*28 and HO-1 (A-413T) was performed. Acute rejection and graft survival were monitored as end-points.
  
  
  RESULTS
  Serum levels of total bilirubin were significantly increased after transplantation (0.41 ± 0.19 mg/dL to 0.80 ± 0.33 mg/dL, P<0.001). Post-transplant 1-year bilirubin level was higher in 6/7 or 7/7 carriers compared with 6/6 homozygotes in terms of the UGT1A1*28 polymorphism (6/6 vs. 6/7 vs. 7/7: 0.71 ± 0.27 vs. 1.06 ± 0.36 vs. 1.10 ± 0.45 mg/dL, P<0.001). According to an additive model of genotype analysis, the 7-allele genotype had a protective effect on the development of acute rejection compared with the 6-allele (odds ratio 0.43, 95% CI 0.25-0.73, P for trend = 0.006). Multivariate Cox regression analysis revealed that individuals carrying the 7-allele had a decreased risk of graft loss, by a factor of 0.36 (95% CI 0.15-0.85, P = 0.019). The HO-1 (A-413T) polymorphism had no effect on serum bilirubin levels or graft outcomes.
  
  
  CONCLUSIONS
  The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation.
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Jung Pyo
authors.initials: JP
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Do Hyoung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Nam
authors.initials: JN
authors.lastname: An
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sang Il
authors.initials: SI
authors.lastname: Min
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jongwon
authors.initials: J
authors.lastname: Ha
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Yun Kyu
authors.initials: YK
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Chun Soo
authors.initials: CS
authors.lastname: Lim
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001663:Bilirubin / Q000097:blood*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000099148:UGT1A1 Enzyme
chemical_list: D000975:Antioxidants; D001663:Bilirubin; D014453:Glucuronosyltransferase; D051547:Heme Oxygenase-1; D000099148:UGT1A1 Enzyme