原发性胆汁性胆管炎遗传易感性的研究现状
DOI: 10.12449/JCH240328
Current status of research on the genetic susceptibility of primary biliary cholangitis
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摘要: 原发性胆汁性胆管炎(PBC)是一种以胆管上皮细胞变性坏死为主,好发于中老年女性,具有强烈的遗传倾向性的肝脏自身免疫性疾病。随着全基因组关联分析(GWAS)的不断发展,PBC的遗传易感性备受关注。本文阐述了与PBC密切相关的遗传易感基因的研究进展,以期为PBC治疗提供有效靶点。Abstract: Primary biliary cholangitis (PBC) is a liver autoimmune disease with a strong genetic tendency characterized by the degeneration and necrosis of bile duct epithelial cells, and it is often observed in middle-aged and elderly women. With the continuous development of genome-wide association studies, the genetic susceptibility of PBC has attracted more and more attention. This article elaborates on the research advances in the genetic susceptibility genes closely associated with PBC, in order to provide effective targets for the treatment of PBC.
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表 1 与中国PBC显著相关的易感位点
Table 1. Susceptible loci significantly associated with Chinese PBC
候选基因 基因位置 SNP 组合P值 比值比 (95%可信区间) HLA-DRA 6p21 rs9268644 2.41×10-19 0.51(0.44~0.59) HLA-DPB1 6p21 rs9501251 8.17×10-13 1.94(1.61~2.33) IL1RL1 2q12.1 rs12712133 5.19×10-9 1.14(1.07~1.21) IL-12A 3q25.33 rs485499 4.20×10-2 1.20(1.01~1.44) IL-12RB2 1p31.3 rs11209050 4.00×10-4 1.27(1.11~1.44) CXCR5 11q23.3 rs715412 1.30×10-2 1.26(1.05~1.52) DDX6,CXCR5 11q23.3 rs77871618 9.12×10-14 1.55(1.38~1.74) CCL20 2q36.3 rs4973341 2.34×10-10 0.82(0.74~0.90) TNFSF15,TNFSF8 9q32 rs4979467 8.28×10-12 1.40(1.27~1.54) TNFRSF1A 12p13.31 rs4149576 1.11×10-5 1.35(1.18~1.55) TNFAIP3 6q23.3 rs6933404 1.27×10-10 1.18(1.09~1.27) ORMDL3,GSDMB,IKZF3 17q12 5.58×10-7 1.381) SNRPGP8 2q36.3 rs4973341 2.34×10-10 0.82(0.74~0.90) ARID3A 19p13.3 rs2238571 5.24×10-10 0.771) FCRL3 1q32.1 rs117214467 8.55×10-3 DNMT3A 3q24.2 rs6807549 1.37×10-3 RARB 4q24 rs79109654 8.56×10-5 TRIM14 10q11.23 rs76129863 4.83×10-3 WDFY4 11p15.5 rs3216 8.17×10-2 TMEM163 6q21 rs4134466 6.71×10-7 RPL3,SYNGR1 22q13.1 rs137603 2.06×10-7 0.68(0.59~0.79) HELZ2 20q13.33 rs79267778 1.87×10-4 4.20(1.67~10.58) 注:1)95%可信区间无法获取;SNP,单核苷酸多态性。 -
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