Norwegian PSC Research Center, Medical Department, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Curr Opin Gastroenterol. 2010 May;26(3):251-8. doi: 10.1097/MOG.0b013e328336807d.
Many of the cholestatic diseases show similar clinical features, despite underlying differences in the genetic etiology. The present review aims to present recent insight into this etiological heterogeneity.
Mutations in the genes causing progressive familial intrahepatic cholestasis are also involved in less severe phenotypes like benign recurrent intrahepatic cholestasis, gallstone disease, intrahepatic cholestasis of pregnancy and drug-induced cholestasis. This probably represents a continuum of severity of the mutations involved, but also complex patterns of inheritance ranging from monogenic autosomal recessive disorders to heterozygosity only conferring a moderate increase in disease risk, where additional genetic or environmental factors are needed to acquire a disease phenotype. Recent genome-wide association studies in the inflammatory cholestatic diseases primary biliary cirrhosis and primary sclerosing cholangitis have revealed susceptibility genes involved in autoimmunity and inflammatory bowel disease, whereas the genetic risk factors for the biliary preference of these diseases remain unknown.
The complexity of the genetic contribution to cholestatic liver disease needs to be accounted for to fully understand the pathogenesis of these conditions.
尽管在遗传病因学上存在差异，但许多胆汁淤积性疾病表现出相似的临床特征。本综述旨在介绍该病因异质性的最新见解。
导致进行性家族性肝内胆汁淤积症的基因突变也与较轻的表型有关，如良性复发性肝内胆汁淤积症、胆石症、妊娠肝内胆汁淤积症和药物性胆汁淤积症。这可能代表了所涉及突变严重程度的连续体，也代表了从单基因常染色体隐性疾病到仅杂合性赋予疾病风险中度增加的复杂遗传模式，其中需要额外的遗传或环境因素才能获得疾病表型。最近在炎症性胆汁淤积性疾病原发性胆汁性胆管炎和原发性硬化性胆管炎中的全基因组关联研究揭示了自身免疫和炎症性肠病相关的易感性基因，而这些疾病对胆管的遗传风险因素仍不清楚。
遗传因素对胆汁淤积性肝病的复杂性需要加以考虑，以充分了解这些疾病的发病机制。
