|Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients.|
|PMID: 21411679 Owner: NLM Status: MEDLINE|
|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.
|Ying-Hwa Chen; Szu-Chun Hung; Der-Cherng Tarng|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|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|
|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|
|Languages: eng Pagination: 567-74 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Analysis of Variance
Bilirubin / blood*
Biological Markers / blood
Cardiovascular Diseases / blood, etiology*, genetics, mortality
Genetic Predisposition to Disease
Glucuronosyltransferase / genetics*
Kidney Diseases / blood, complications, genetics, mortality, therapy*
Proportional Hazards Models
Renal Dialysis* / adverse effects, mortality
|0/Biological Markers; EC 2.4.1.-/UGT1A1 enzyme; EC 220.127.116.11/Glucuronosyltransferase; RFM9X3LJ49/Bilirubin|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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