title: Association between the UGT1A1 TA-repeat polymorphism and bilirubin concentration in patients with intermittent claudication: results from the CAVASIC study.
abstract: BACKGROUND
  Bilirubin has antioxidative and cytoprotective properties. Low plasma concentrations of bilirubin are reportedly associated with the development of coronary and cerebrovascular disease, and bilirubin concentrations are strongly correlated with the enzyme activity of the hepatic uridine diphosphate glucuronosyltransferase (UGT1A1). The activity of UGT1A1 is influenced by a TA-repeat polymorphism in the promoter of the UGT1A1 gene (UDP glucuronosyltransferase 1 family, polypeptide A1). In a case-control study, we investigated the association between the UGT1A1 polymorphism, bilirubin concentration, and intermittent claudication.
  
  
  METHODS
  We included 255 consecutive male patients presenting with intermittent claudication in the investigation and matched the patients by age and diabetes mellitus with 255 control individuals.
  
  
  RESULTS
  Plasma bilirubin concentrations were significantly lower in patients than in controls [mean (SD), 12.5 (5.3) micromol/L vs 15.4 (7.9) micromol/L; P < 0.001]. We found a clear association between the number of TA repeats and plasma bilirubin concentration. Considering the 6/6 TA-repeat genotype as the wild type, we observed a slight increase in bilirubin concentration individuals with the heterozygous 6/7 genotype and pronounced increases for those with the homozygous 7/7 genotype. This association occurred in both controls and patients; however, patients and controls were not significantly different with respect to UGT1A1 TA-repeat genotype frequencies.
  
  
  CONCLUSIONS
  Our study of a well-phenotyped group of patients with intermittent claudication and control individuals revealed a clear association between low bilirubin concentrations and peripheral arterial disease but no association between the UGT1A1 polymorphism and the disease.
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Barbara
authors: B
authors: Rantner
authors: Barbara
authors: B
authors: Kollerits
authors: Marietta
authors: M
authors: Anderwald-Stadler
authors: Peter
authors: P
authors: Klein-Weigel
authors: Ingrid
authors: I
authors: Gruber
authors: Anke
authors: A
authors: Gehringer
authors: Markus
authors: M
authors: Haak
authors: Mirjam
authors: M
authors: Schnapka-Köpf
authors: Gustav
authors: G
authors: Fraedrich
authors: Florian
authors: F
authors: Kronenberg
mesh_terms: D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood*; D016022:Case-Control Studies; D018900:Dinucleotide Repeats; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007383:Intermittent Claudication / Q000235:genetics* / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme