Inherited Disorders of Bilirubin Transport and Conjugation: New Insights Into Molecular Mechanisms and Consequences
Inherited Disorders of Bilirubin Transport and Conjugation: New Insights Into Molecular Mechanisms and Consequences
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DOI：
10.1053/j.gastro.2014.03.047
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发表时间：
2014-06-01
期刊：
影响因子：
29.4
通讯作者：
Dhumeaux, Daniel
中科院分区：
文献类型：
--
作者：
Erlinger, Serge;Arias, Irwin M.;Dhumeaux, Daniel
胆红素代谢的遗传性疾病可能会减少肝细胞对胆红素的摄取、胆红素结合或胆红素分泌到胆汁中。摄取减少可增加未结合或结合胆红素水平（Rotor综合征）。胆红素结合缺陷可增加非结合胆红素水平;影响可能是良性和频繁的（吉尔伯特综合征）或罕见但严重的，增加胆红素脑病的风险（Crigler-Najjar综合征）。胆红素分泌障碍导致结合胆红素蓄积（Dubin-Johnson综合征）。我们回顾了胆红素转运和结合障碍的遗传原因和病理生理学，以及临床和治疗方面。我们还讨论了高胆红素血症预防心血管疾病和代谢综合征的可能机制，以及特定遗传变异对药物代谢和癌症发展的影响。
Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in uptake could increase levels of unconjugated or conjugated bilirubin (Rotor syndrome). Defects in bilirubin conjugation could increase levels of unconjugated bilirubin; the effects can be benign and frequent (Gilbert syndrome) or rare but severe, increasing the risk of bilirubin encephalopathy (Crigler-Najjar syndrome). Impairment of bilirubin secretion leads to accumulation of conjugated bilirubin (Dubin-Johnson syndrome). We review the genetic causes and pathophysiology of disorders of bilirubin transport and conjugation as well as clinical and therapeutic aspects. We also discuss the possible mechanisms by which hyperbilirubinemia protects against cardiovascular disease and the metabolic syndrome and the effects of specific genetic variants on drug metabolism and cancer development.