| Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients. | |
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MedLine Citation:
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PMID: 21411679 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND OBJECTIVES: Bilirubin is a protective factor with antioxidant and anti-inflammatory properties, but its association with clinical outcomes of hemodialysis patients is unknown. Bilirubin degradation is mainly determined by the activity of hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1), which is significantly influenced by a TA-repeat polymorphism in the gene's promoter, an allele designated UGT1A1*28. The study aimed to clarify the association between serum bilirubin and UGT1A1*28 polymorphism and their respective effect on outcomes of chronic hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The cohort study comprised 661 chronic hemodialysis patients who were prospectively followed for 12 years. The endpoints were cardiovascular events (CVEs) and all-cause mortality. RESULTS: After adjustment for traditional and dialysis-related risk factors, individuals with bilirubin in the upper tertile had an adjusted hazard ratio of 0.32 for CVEs and 0.48 for all-cause mortality compared with those in the lower tertile. Individuals homozygous for UGT1A1*28 (genotype 7/7) had significantly higher bilirubin levels than those with 6/6 and 7/6 genotypes. In the same multivariable-adjusted model, individuals with 7/7 had approximately one tenth the risk for CVEs and one fourth the risk for all-cause mortality as compared with carriers of the 6 allele. CONCLUSIONS: A graded, reverse association was noted between serum bilirubin and adverse outcomes among chronic hemodialysis patients. Moreover, the UGT1A1*28 polymorphism had strong effects on bilirubin levels and the 7/7 genotype might have an important effect on reducing CVEs and death. |
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Authors:
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Ying-Hwa Chen; Szu-Chun Hung; Der-Cherng Tarng |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical journal of the American Society of Nephrology : CJASN Volume: 6 ISSN: 1555-905X ISO Abbreviation: Clin J Am Soc Nephrol Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-17 Completed Date: 2011-06-30 Revised Date: 2012-09-19 |
Medline Journal Info:
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Nlm Unique ID: 101271570 Medline TA: Clin J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 567-74 Citation Subset: IM |
Affiliation:
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Department of Medicine, National Yang-Ming University, Taipei, Nil 11217, Taiwan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Analysis of Variance Bilirubin / blood* Biological Markers / blood Cardiovascular Diseases / blood, etiology*, genetics, mortality Chi-Square Distribution Chronic Disease Female Follow-Up Studies Gene Frequency Genetic Predisposition to Disease Glucuronosyltransferase / genetics* Homozygote Humans Kaplan-Meier Estimate Kidney Diseases / blood, complications, genetics, mortality, therapy* Male Middle Aged Phenotype Polymorphism, Genetic* Proportional Hazards Models Prospective Studies Renal Dialysis* / adverse effects, mortality Risk Assessment Risk Factors Taiwan Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 635-65-4/Bilirubin; EC 2.4.1.-/bilirubin uridine-diphosphoglucuronosyl transferase 1A1; EC 2.4.1.17/Glucuronosyltransferase |
| Comments/Corrections | |
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