Carlton Victoria E H, Pawlikowska Ludmila, Bull Laura N
Liver Center Laboratory and Department of Medicine, San Francisco General Hospital, San Francisco, California 94110, USA.
Ann Med. 2004;36(8):606-17. doi: 10.1080/07853890410018916.
Intrahepatic cholestasis, or impairment of bile flow, is an important manifestation of inherited and acquired liver disease. In recent years, human genetic and molecular studies have identified several genes, the disruption of which results in cholestasis. ATP8B1 (FIC1), ABCB11 (BSEP), and ABCB4 (MDR3) are disrupted in forms of progressive familial intrahepatic cholestasis (PFIC) and related disorders. Mutations in BAAT, TJP2 (ZO-2), and EPHX1 have been identified in patients with hypercholanemia. A CLDN1 mutation was recently reported in patients with ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis (ILVASC), and North American Indian childhood cirrhosis (NAIC) is associated with a missense mutation in CIRH1A. Alagille syndrome patients carry mutations in JAG1, and mutations in VPS33B have been identified in patients with arthrogryposis, renal dysfunction and cholestasis syndrome (ARC). Identification of these genes, and characterization of the proteins they encode, is enhancing our understanding of the biology of the enterohepatic circulation in health and disease.
肝内胆汁淤积，即胆汁流动受损，是遗传性和获得性肝病的重要表现。近年来，人类遗传学和分子研究已经鉴定出几个基因，其破坏会导致胆汁淤积。ATP8B1（FIC1）、ABCB11（BSEP）和ABCB4（MDR3）在进行性家族性肝内胆汁淤积（PFIC）及相关疾病中遭到破坏。在高胆汁血症患者中已鉴定出BAAT、TJP2（ZO-2）和EPHX1的突变。最近在鱼鳞病、白细胞空泡、脱发和硬化性胆管炎（ILVASC）患者中报道了CLDN1突变，北美印第安儿童肝硬化（NAIC）与CIRH1A中的错义突变有关。阿拉吉耶综合征患者携带JAG1突变，在关节挛缩、肾功能不全和胆汁淤积综合征（ARC）患者中已鉴定出VPS33B突变。这些基因的鉴定及其编码蛋白质的表征，正在加深我们对健康和疾病状态下肝肠循环生物学的理解。
