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.

journal_name

Clin Chem

journal_title

Clinical chemistry

authors

Rantner B,Kollerits B,Anderwald-Stadler M,Klein-Weigel P,Gruber I,Gehringer A,Haak M,Schnapka-Köpf M,Fraedrich G,Kronenberg F

doi

10.1373/clinchem.2007.102046

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

851-7

issue

5

eissn

0009-9147

issn

1530-8561

pii

clinchem.2007.102046

journal_volume

54

pub_type

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