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Molecular Diagnostics and Genetics: Barbara Rantner, Barbara Kollerits, Marietta Anderwald-Stadler, Peter Klein-Weigel, Ingrid Gruber, Anke Gehringer, Markus Haak, Mirjam Schnapka-Köpf, Gustav Fraedrich, and Florian Kronenberg Association between the UGT1A1 TA-Repeat Polymorphism and Bilirubin Concentration in Patients with Intermittent Claudication: Results from the CAVASIC Study Clin Chem 2008; 0: clinchem.2007.102046v1 [Abstract] [PDF]

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UGT1A1, plasma bilirubin and peripheral artery disease

Libor Vitek, Harvey A. Schwertner; Clinical Research, Wilford Hall Medical Center, San Antonio, Texas   (1 May 2008)

UGT1A1, plasma bilirubin and peripheral artery disease 1 May 2008
Libor Vitek 1st Faculty of Medicine, Charles University in Prague, Czech Republic, Harvey A. Schwertner; Clinical Research, Wilford Hall Medical Center, San Antonio, Texas Send letter to journal: Re: UGT1A1, plasma bilirubin and peripheral artery disease vitek{at}cesnet.cz Libor Vitek, et al.	Dear Sir; We read with interest the recent paper by Rantner et al. on the association between UGT1A1, plasma bilirubin concentrations, and peripheral artery disease (PAD) (1). This study provides additional supporting evidence that plasma and serum bilirubin concentrations are inversely related to atherosclerosis. Since the majority of previously published studies have studied cardiovascular disease presence in individuals with serum bilirubin concentrations in the normal range, it would be interesting to see the results of Rantner’s studies comparing the odds ratios in both cases and controls with bilirubin concentrations above 1 mg/dL (17 mmol/L, a phenotypic sign of Gilbert syndrome). If a protective effect of slightly increased bilirubin is found in individuals with PAD, the findings would support the protective role of increased bilirubin previously found in individuals with Gilbert syndrome (2). Even though not mentioned, the negative association between the UGT1A1 polymorphism and incidence of PAD could result from the low penetrance (50%) of UGT1A1*28 allele, the Gilbert´s polymorphism. Therefore, homozygosity of the UGT1A1*28 allele might exert its protective effect only if it is associated with increased serum bilirubin concentrations. This same reasoning might account for the negative results of the previous Rotterdam and ECTIM studies (3). It also should be noted that reverse causality, i.e. disease-mediated consumption of anti-oxidatively acting bilirubin, might be a causal factor in the association between low plasma bilirubin concentrations and incidence of PAD. Therefore, analysis of bilirubin variance explained by various factors should be performed on the whole population (cases+controls) and the presence of PAD should be evaluated as an additional variable which could account for the decreased serum bilirubin concentrations. Such analysis would support a reverse causality hypothesis since the plasma concentrations of bilirubin were found to be substantially lower in subjects with PAD than in those without PAD. Grant/Funding Support: Supported by grant MSM 0021620807 from the Czech Ministry of Education. Financial Disclosures: None to declare Acknowledgements: n/a References 1. Rantner B, Kollerits B, Anderwald-Stadler M, Klein-Weigel P, Gruber I, Gehringer A, et al. Association between the UGT1A1 TA-repeat polymorphism and bilirubin concentration in patients with intermittent claudication: results from the CAVASIC study. Clin Chem 2008;Mar 28 [Epub ahead of print]. 2. Vítek L, Novotný L, Šperl M, Holaj R, Spáčil J. The inverse association of elevated serum bilirubin levels with subclinical carotid atherosclerosis. Cerebrovasc Dis 2006;21:408-14. 3. Schwertner HA, Vítek L. Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin. Atherosclerosis 2008;198:1-11.