title: Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Medicine, National Yang-Ming University, Taipei, Nil 11217, Taiwan.
authors.forename: Ying-Hwa
authors.initials: YH
authors.lastname: Chen
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hung
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan; D013997:Time Factors; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D015415:Biomarkers; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme