A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.
A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.
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一项全基因组关联研究确定了原发性胆汁性胆管炎的六个新风险位点。
DOI：
10.1038/ncomms14828
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发表时间：
2017-04-20
影响因子：
16.6
通讯作者：
Ma X
中科院分区：
文献类型：
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作者：
Qiu F;Tang R;Zuo X;Shi X;Wei Y;Zheng X;Dai Y;Gong Y;Wang L;Xu P;Zhu X;Wu J;Han C;Gao Y;Zhang K;Jiang Y;Zhou J;Shao Y;Hu Z;Tian Y;Zhang H;Dai N;Liu L;Wu X;Zhao W;Zhang X;Zang Z;Nie J;Sun W;Zhao Y;Mao Y;Jiang P;Ji H;Dong Q;Li J;Li Z;Bai X;Li L;Lin M;Dong M;Li J;Zhu P;Wang C;Zhang Y;Jiang P;Wang Y;Jawed R;Xu J;Zhang Y;Wang Q;Yang Y;Yang F;Lian M;Jiang X;Xiao X;Li Y;Fang J;Qiu D;Zhu Z;Qiu H;Zhang J;Tian W;Chen S;Jiang L;Ji B;Li P;Chen G;Wu T;Sun Y;Yu J;Tang H;He M;Xia M;Pei H;Huang L;Qing Z;Wu J;Huang Q;Han J;Xie W;Sun Z;Guo J;He G;Eric Gershwin M;Lian Z;Liu X;Seldin MF;Liu X;Chen W;Ma X
原发性胆道胆管炎（PBC）是一种具有强烈遗传成分的自身免疫性肝病。在这里，我们报告了一项全基因组关联研究，包括1,122例PBC病例和4,036例汉族对照，随后在907例PBC病例和2,127例对照的单独队列中重复。我们的研究结果显示了14个PBC风险位点的全基因组关联，包括先前确定的6p 21（HLA-DR和DPB 1），17 q12（ORMDL 3），3q13.33（CD 80），2q32.3（STAT 1/STAT 4），3q25.33（IL 12 A），4 q24（NF-κB）和22q13.1（RPL 3/SYNGR 1）。我们还鉴定了IL 21、IL 21 R、CD 28/CTLA 4/ICOS、CD 58、ARID 3A和IL 16中的变体作为新的PBC风险基因座。这些新的发现和组织化学研究表明PBC肝脏（特别是肝门静脉轨道）中IL 21和IL 21 R的表达增强，这支持了一种疾病机制，其中除了CD 4 T细胞活化和T细胞共刺激之外，IL 21信号传导途径的失调是PBC发展的关键组成部分。原发性胆管炎是一种自身免疫性肝病。在这里，作者表明，白细胞介素基因的变异，可能解除其表达与这种情况有关，并表明IL 21信号通路可能在疾病病因中发挥作用。
Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13.1 (RPL3/SYNGR1). We also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC. Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.