Karlsen Tom-H, Schrumpf Erik, Boberg Kirsten-Muri
Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway.
World J Gastroenterol. 2007 Nov 7;13(41):5421-31. doi: 10.3748/wjg.v13.i41.5421.
The aetiology of primary sclerosing cholangitis (PSC) is not known. A more than 80-fold increased risk of PSC among first-degree relatives emphasizes the importance of genetic factors. Genetic associations within the human leukocyte antigen (HLA) complex on chromosome 6p21 were detected in PSC 25 years ago. Subsequent studies have substantiated beyond doubt that one or more genetic variants located within this genetic region are important. The true identities of these variants, however, remain to be identified. Several candidate genes at other chromosomal loci have also been investigated. However, according to strict criteria for what may be denominated a susceptibility gene in complex diseases, no such gene exists for PSC today. This review summarises present knowledge on the genetic susceptibility to PSC, as well as genetic associations with disease progression and clinical subsets of particular interest (inflammatory bowel disease and cholangiocarcinoma).
原发性硬化性胆管炎（PSC）的病因尚不清楚。一级亲属中PSC的发病风险增加80倍以上，这凸显了遗传因素的重要性。25年前在PSC患者中检测到位于6号染色体p21区域的人类白细胞抗原（HLA）复合体存在遗传关联。随后的研究毫无疑问地证实，位于该遗传区域内的一个或多个基因变异很重要。然而，这些变异的真正身份仍有待确定。其他染色体位点的几个候选基因也已被研究。然而，根据复杂疾病中可能被称为易感基因的严格标准，目前PSC不存在这样的基因。这篇综述总结了目前关于PSC遗传易感性的知识，以及与疾病进展和特别感兴趣的临床亚组（炎症性肠病和胆管癌）的遗传关联。
