Tags

Type your tag names separated by a space and hit enter

Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients.
Clin J Am Soc Nephrol. 2011 Mar; 6(3):567-74.CJ

Abstract

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+Show Affiliations

Department of Medicine, National Yang-Ming University, Taipei, Nil 11217, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21411679

Citation

Chen, Ying-Hwa, et al. "Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients." Clinical Journal of the American Society of Nephrology : CJASN, vol. 6, no. 3, 2011, pp. 567-74.
Chen YH, Hung SC, Tarng DC. Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients. Clin J Am Soc Nephrol. 2011;6(3):567-74.
Chen, Y. H., Hung, S. C., & Tarng, D. C. (2011). Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients. Clinical Journal of the American Society of Nephrology : CJASN, 6(3), 567-74. https://doi.org/10.2215/CJN.06130710
Chen YH, Hung SC, Tarng DC. Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients. Clin J Am Soc Nephrol. 2011;6(3):567-74. PubMed PMID: 21411679.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients. AU - Chen,Ying-Hwa, AU - Hung,Szu-Chun, AU - Tarng,Der-Cherng, PY - 2011/3/18/entrez PY - 2011/3/18/pubmed PY - 2011/7/1/medline SP - 567 EP - 74 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 6 IS - 3 N2 - 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. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/21411679/Serum_bilirubin_links_UGT1A1_28_polymorphism_and_predicts_long_term_cardiovascular_events_and_mortality_in_chronic_hemodialysis_patients_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=21411679 DB - PRIME DP - Unbound Medicine ER -