Document Detail


Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients.
MedLine Citation:
PMID:  21411679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ying-Hwa Chen; Szu-Chun Hung; Der-Cherng Tarng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2011-03-17     Completed Date:  2011-06-30     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  101271570     Medline TA:  Clin J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  567-74     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
0/Biological Markers; EC 2.4.1.-/UGT1A1 enzyme; EC 2.4.1.17/Glucuronosyltransferase; RFM9X3LJ49/Bilirubin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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