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This Article Full Text Full Text (PDF) All Versions of this Article: clinchem.2007.102046v1 54/5/851    most recent Submit an electronic Letter to the Editor about this paper View responses Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rantner, B. Articles by Kronenberg, F. Search for Related Content PubMed PubMed Citation Articles by Rantner, B. Articles by Kronenberg, F. Related Collections Molecular Diagnostics and Genetics

Association between the UGT1A1 TA-Repeat Polymorphism and Bilirubin Concentration in Patients with Intermittent Claudication: Results from the CAVASIC Study

¹ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria; ² Department of Vascular Surgery, Innsbruck Medical University, Innsbruck, Austria; ³ 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria; ⁴ DRK-Klinik Mark Brandenburg, Department of Angiology, Berlin, Germany; ⁵ Central Laboratory for Medical and Chemical Laboratory Diagnostics, Innsbruck Medical University, Innsbruck, Austria.

^aAddress correspondence to this author at: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria. Fax (43) 512 9003-73560 or (43) 512 9003-73561; e-mail Florian.Kronenberg{at}i-med.ac.at.

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) µmol/L vs 15.4 (7.9) µmol/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.

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