Rantner Barbara, Kollerits Barbara, Anderwald-Stadler Marietta, Klein-Weigel Peter, Gruber Ingrid, Gehringer Anke, Haak Markus, Schnapka-Köpf Mirjam, Fraedrich Gustav, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Clin Chem. 2008 May;54(5):851-7. doi: 10.1373/clinchem.2007.102046. Epub 2008 Mar 28.
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.
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.
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.
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.
胆红素具有抗氧化和细胞保护特性。据报道，血浆胆红素浓度低与冠状动脉和脑血管疾病的发生有关，且胆红素浓度与肝脏尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1）的酶活性密切相关。UGT1A1的活性受UGT1A1基因（尿苷二磷酸葡萄糖醛酸转移酶1家族，多肽A1）启动子中TA重复多态性的影响。在一项病例对照研究中，我们调查了UGT1A1多态性、胆红素浓度与间歇性跛行之间的关联。
我们纳入了255例连续的出现间歇性跛行的男性患者进行研究，并按年龄和糖尿病情况将这些患者与255名对照个体进行匹配。
患者的血浆胆红素浓度显著低于对照组[均值（标准差），12.5（5.3）μmol/L对15.4（7.9）μmol/L；P<0.001]。我们发现TA重复次数与血浆胆红素浓度之间存在明显关联。将6/6 TA重复基因型视为野生型，我们观察到杂合6/7基因型个体的胆红素浓度略有升高，而纯合7/7基因型个体的胆红素浓度则显著升高。这种关联在对照组和患者中均存在；然而，患者和对照组在UGT1A1 TA重复基因型频率方面无显著差异。
我们对一组明确表型的间歇性跛行患者和对照个体的研究表明，低胆红素浓度与外周动脉疾病之间存在明显关联，但UGT1A1多态性与该疾病之间无关联。
