原发性胆汁性胆管炎的遗传学研究现状

Advances in genetic research on primary biliary cholangitis

原发性胆汁性胆管炎(PBC)是一种具有明显遗传易感性的自身免疫性肝病。近年来开展的全基因组关联分析和基因芯片等遗传学研究,在揭示PBC的发病机制中发挥着重要的作用。PBC的易感基因主要分为人类白细胞抗原基因和非人类白细胞抗原基因两大类,其易感位点大多与免疫调节相关,表明免疫调节通路紊乱可能在PBC的发病中起关键作用。此外,这些候选基因的加权基因风险评分在一定程度上可能预测PBC的发病风险。如今,约有1/3的PBC患者对现有的PBC标准治疗药物熊去氧胆酸反应不佳。因此,易感基因对应的靶向药物有望成为有效的替代疗法。

Primary biliary cholangitis（PBC） is an autoimmune liver disease with strong genetic susceptibility.The genome-wide association studies and immunochip studies conducted in recent years help to reveal the pathogenesis of PBC.The susceptibility genes of PBC are classified into human leukocyte antigen gene and non-human leukocyte antigen gene,and most of the susceptibility loci are associated with immune regulation,suggesting that disorders of the immune regulatory pathways may play an important role in the pathogenesis of PBC.In addition,the weighted genetic risk score of these candidate genes may predict the risk of PBC.At present,about one third of PBC patients have suboptimal response to ursodeoxycholic acid;therefore,targeted drugs for susceptibility genes may become an effective substitutive therapy.