Lingenhel Arno, Kollerits Barbara, Schwaiger Johannes P, Hunt Steven C, Gress Richard, Hopkins Paul N, Schoenborn Veit, Heid Iris M, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstrasse 41, A-6020 Innsbruck, Austria.
Exp Gerontol. 2008 Dec;43(12):1102-7. doi: 10.1016/j.exger.2008.08.047. Epub 2008 Aug 26.
Low levels of the antioxidative serum bilirubin are associated with vascular aging and an increased risk for coronary artery disease (CAD). UGT1A1 is the major gene influencing bilirubin concentrations. Therefore, we investigated an association of bilirubin levels and two polymorphisms in the promoter of UGT1A1 (-53(TA-repeat) polymorphism and T-3279G) in 477 patients with premature, familial CAD and 619 age- and sex-matched controls. Bilirubin concentrations were significantly lower in cases than in controls (0.62+/-0.36 vs. 0.76+/-0.41 mg/dl for men, p=1.2 x 10(-10); and 0.42+/-0.29 vs. 0.55+/-0.23 mg/dl, p=1.9 x 10(-9) for women). Both polymorphisms showed a strong association with bilirubin levels with higher levels for homozygote carriers of the minor allele. These associations were most pronounced in male controls and patients (p=5.9 x 10(-26) and p=3.4 x 10(-16), respectively, for the -53(TA-repeat) polymorphism). Logistic regression analysis revealed low bilirubin levels but not the UGT1A1 polymorphisms to be significantly associated with CAD: OR (95% CI) 0.90 (0.86-0.94), p=2.6 x 10(-6) for men and 0.77 (0.68-0.87), p=3.2 x 10(-5) for women, respectively for each 0.1mg/dl increase of bilirubin. These results indicate that it is rather decreased bilirubin levels in general than the changes in the genetic variation of this gene that increase the risk for CAD.
血清抗氧化胆红素水平较低与血管老化及冠状动脉疾病（CAD）风险增加相关。UGT1A1是影响胆红素浓度的主要基因。因此，我们在477例早发家族性CAD患者及619例年龄和性别匹配的对照中，研究了胆红素水平与UGT1A1启动子区两个多态性（-53（TA重复）多态性和T-3279G）之间的关联。病例组的胆红素浓度显著低于对照组（男性：0.62±0.36 vs. 0.76±0.41mg/dl，p = 1.2×10⁻¹⁰；女性：0.42±0.29 vs. 0.55±0.23mg/dl，p = 1.9×10⁻⁹）。两种多态性均与胆红素水平密切相关，次要等位基因纯合子携带者的胆红素水平更高。这些关联在男性对照组和患者中最为明显（-53（TA重复）多态性在男性对照组和患者中的p值分别为5.9×10⁻²⁶和3.4×10⁻¹⁶）。逻辑回归分析显示，低胆红素水平而非UGT1A1多态性与CAD显著相关：男性中，胆红素每增加0.1mg/dl，OR（95%CI）为0.90（0.86 - 0.94），p = 2.6×10⁻⁶；女性中，OR（95%CI）为0.77（0.68 - 0.87），p = 3.2×10⁻⁵。这些结果表明，增加CAD风险的是总体胆红素水平的降低，而非该基因遗传变异的改变。
