Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation.
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 varia...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3972238?pdf=render |
| _version_ | 1818217612869369856 |
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| author | Jung Pyo Lee Do Hyoung Kim Seung Hee Yang Jin Ho Hwang Jung Nam An Sang Il Min Jongwon Ha Yun Kyu Oh Yon Su Kim Chun Soo Lim |
| author_facet | Jung Pyo Lee Do Hyoung Kim Seung Hee Yang Jin Ho Hwang Jung Nam An Sang Il Min Jongwon Ha Yun Kyu Oh Yon Su Kim Chun Soo Lim |
| author_sort | Jung Pyo Lee |
| collection | DOAJ |
| description | 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.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.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.The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation. |
| first_indexed | 2024-12-12T07:10:39Z |
| format | Article |
| id | doaj.art-f53eae66ca63462f990b6254582d4356 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T07:10:39Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f53eae66ca63462f990b6254582d43562022-12-22T00:33:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9363310.1371/journal.pone.0093633Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation.Jung Pyo LeeDo Hyoung KimSeung Hee YangJin Ho HwangJung Nam AnSang Il MinJongwon HaYun Kyu OhYon Su KimChun Soo LimOxidative 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.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.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.The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation.http://europepmc.org/articles/PMC3972238?pdf=render |
| spellingShingle | Jung Pyo Lee Do Hyoung Kim Seung Hee Yang Jin Ho Hwang Jung Nam An Sang Il Min Jongwon Ha Yun Kyu Oh Yon Su Kim Chun Soo Lim Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation. PLoS ONE |
| title | Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation. |
| title_full | Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation. |
| title_fullStr | Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation. |
| title_full_unstemmed | Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation. |
| title_short | Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation. |
| title_sort | serum bilirubin affects graft outcomes through udp glucuronosyltransferase sequence variation in kidney transplantation |
| url | http://europepmc.org/articles/PMC3972238?pdf=render |
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