Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients
Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients
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DOI：
10.2215/cjn.06130710
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发表时间：
2011-03-01
影响因子：
9.8
通讯作者：
Tarng, Der-Cherng
中科院分区：
文献类型：
--
作者：
Chen, Ying-Hwa;Hung, Szu-Chun;Tarng, Der-Cherng
背景与目的胆红素是一种具有抗氧化和抗炎作用的保护因子，但其与血液透析患者临床结局的关系尚不清楚。胆红素降解主要由肝胆红素尿苷二磷酸-葡萄糖醛酸转移酶（UGT 1A 1）的活性决定，该活性受到该基因启动子中TA重复多态性的显著影响，该等位基因被命名为UGT 1A 1 *28。本研究旨在阐明血清胆红素和UGT 1A 1 *28多态性之间的关联及其各自对慢性血液透析患者结局的影响。设计、设置、参与者和测量队列研究包括661例慢性血液透析患者，前瞻性随访12年。终点是心血管事件（CVEs）和全因死亡率。结果在调整传统和透析相关的危险因素后，与UGT 1A 1 *28纯合子的低三分位数个体相比，胆红素水平在上三分位数的个体的CVEs校正风险比为0.32，全因死亡率校正风险比为0.48（7/7）基因型组胆红素水平显著高于6/6和7/6基因型组。在相同的多变量调整模型中，7/7的个体与6等位基因携带者相比，约十分之一的心血管事件风险和四分之一的全因死亡风险。结论慢性血液透析患者血清胆红素和不良结局之间存在分级的反向关联。此外，UGT 1A 1 *28多态性对胆红素水平有很强的影响，7/7基因型可能对减少CVE和死亡有重要影响。Clin J Ant Soc Nephrol 6：567-574，2011. doi：10.2215/CJN.06130710
Background and objectives Bilirubin is a protective factor with antioxidant and anti-inflammatory properties, but its association with clinical outcomes of hemodialysis patients is unknown. Bilirubin degradation is mainly determined by the activity of hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1), which is significantly influenced by a TA-repeat polymorphism in the gene's promoter, an allele designated UGT1A1*28. The study aimed to clarify the association between serum bilirubin and UGT1A1*28 polymorphism and their respective effect on outcomes of chronic hemodialysis patients.Design, setting, participants, & measurements The cohort study comprised 661 chronic hemodialysis patients who were prospectively followed for 12 years. The endpoints were cardiovascular events (CVEs) and all-cause mortality.Results After adjustment for traditional and dialysis-related risk factors, individuals with bilirubin in the upper tertile had an adjusted hazard ratio of 0.32 for CVEs and 0.48 for all-cause mortality compared with those in the lower tertile Individuals homozygous for UGT1A1*28 (genotype 7/7) had significantly higher bilirubin levels than those with 6/6 and 7/6 genotypes. In the same multivariable-adjusted model, individuals with 7/7 had approximately one tenth the risk for CVEs and one fourth the risk for all-cause mortality as compared with carriers of the 6 allele.Conclusions A graded, reverse association was noted between serum bilirubin and adverse outcomes among chronic hemodialysis patients. Moreover, the UGT1A1*28 polymorphism had strong effects on bilirubin levels and the 7/7 genotype might have an important effect on reducing CVEs and death. Clin J Ant Soc Nephrol 6: 567-574, 2011. doi: 10.2215/CJN.06130710