aDivision of Cancer Medicine, Surgery and Transplantation, Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet bDivision of Cancer Medicine, Surgery and Transplantation, K.G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo cDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
Curr Opin Gastroenterol. 2014 May;30(3):310-9. doi: 10.1097/MOG.0000000000000052.
The pathogenesis of primary sclerosing cholangitis (PSC) involves heritable factors. This review summarizes the recent genetic studies and discusses the implications of identified risk loci.
A total of 16 PSC susceptibility loci have been identified in genome-wide association studies and related study designs. At least 33 additional loci are involved in what is increasingly acknowledged to represent a general pool of genetic risk loci for immune-mediated diseases. One important group of genes is part of well characterized immune pathways (e.g. interleukin 2 signaling), whereas for other loci the relationship to PSC pathophysiology is less evident. Importantly, the loci collectively account for only 7.3% of overall PSC liability, thus pointing to a large contribution from environmental factors to PSC development. The individual PSC risk genes cannot be interpreted within a simple cause-effect model used for monogenic traits, but need to be explored for their individual biological correlates, preferably in a disease context. To some extent, as exemplified for the human leukocyte antigen and FUT2 associations, genetic findings may guide the discovery of interacting and co-occuring environmental susceptibility factors.
Multiple PSC susceptibility loci are now available for exploration in experimental model systems and patient-centered research.
原发性硬化性胆管炎（PSC）的发病机制涉及遗传因素。本综述总结了最近的遗传研究，并讨论了已确定的风险基因座的意义。
全基因组关联研究和相关研究设计已确定了 16 个 PSC 易感性基因座。至少还有 33 个额外的基因座涉及越来越被认为是免疫介导性疾病遗传风险基因座的一般池。一组重要的基因是特征明确的免疫途径的一部分（例如白细胞介素 2 信号转导），而对于其他基因座，与 PSC 病理生理学的关系则不那么明显。重要的是，这些基因座总共仅占 PSC 总易感性的 7.3%，这表明环境因素对 PSC 发病机制有很大贡献。个体 PSC 风险基因不能用单基因性状的简单因果模型来解释，而需要在疾病背景下探索其个体生物学相关性。在某种程度上，正如人类白细胞抗原和 FUT2 相关性的例子所示，遗传发现可能有助于发现相互作用和共同发生的环境易感性因素。
现在有多个 PSC 易感性基因座可供实验模型系统和以患者为中心的研究探索。
